Certain 2-phenyl-4-oxo-nicotinates and their use for inducing male sterility in a cereal grain plant

ABSTRACT

This invention relates to compounds of the formula: ##STR1## wherein R 1  is an optionally substituted alkyl or alkenyl group; at least one of R 2 , R 5  and R 6  is ##STR2## wherein (1) when R 2  is ##STR3##  R 5  is a hydrogen atom, an alkyl group or a halogen atom and R 6  is a hydrogen atom or an alkyl group, 
     (2) when R 5  is ##STR4##  R 2  is an alkyl group and R 6  is a hydrogen atom or an alkyl group, 
     (3) when R 6  is ##STR5##  R 2  is an optionally substituted (C 1  -C 6 ) alkyl or a (C 3  -C 6 ) alkenyl group and R 5  is a hydrogen atom, a (C 1  -C 6 ) alkyl group or a halogen atom, and 
     (4) when R 2  and R 6  are both independently ##STR6##  R 5  is a hydrogen atom or an alkyl group; Y is a hydrogen atom or an alkyl group; X is a hydrogen atom, a halogen atom, a trihalomethyl group and the like; and n is an integer from 1 to 3; or the agronomically acceptable alkali metal or acid addition salts thereof. These compounds are useful as chemical hybridization agents on moncotyledonous crops and are especially effective in wheat, corn, barley, rice, rye, triticale and forage crops.

This application is a continuation of application Ser. No. 260,577,filed May 5, 1981, which is a continuation-in-part of application Ser.No. 250,711, filed Apr. 16, 1981, now abandoned, which is acontinuation-in-part of application Ser. No. 148,079, filed May 12,1980, now abandoned.

BACKGROUND OF THE INVENTION

The use of chemical gametocides for the production of new cereal grainsis a rapidly expanding technology. Cereal grain such as corn, wheat,rice, rye, barley, millet, sorghum, triticale and various forage cropsare the main areas where research has been undertaken to improve boththe productivity and the food value of these crops. The utilization ofchemical hybridization agents in this research has made possible thehybridization of cereal grain crops on economical scale. Patents whichpertain to this technology include the Michael C. Seidel patents, U.S.Pat. Nos. 3,761,240; 3,838,155; and 3,576,814, which discloseN-aryl-2-oxonicotinates as male sterilants and plant growth regulators;the Glenn R. Carlson patents, U.S. Pat. Nos. 4,115,101; 4,051,142; andGerman Offen. No. 2,830,700, which disclose the use ofN-aryl-4-oxonicotinate and N-aryl-6-oxonicotinates as male sterilants;and the Taylor patent, U.S. Pat. No. 4,152,136, which discloses the useof 3-aryl-4-pyridones as herbicides. A. Selva and A. Gennaro describe inOrganic Mass Spectrometry, Vol. 11, pp 117-120 (1976) the massspectrometry data for the compound2-phenyl-6-methyl-3-carbethoxy-4-pyridone. No activity is disclosed forthis compound.

Balogh et al., J. Het. Chem., 17, 359 (1980), disclose the synthesis ofvarious 5-substituted (5-aryl)-1-alkyl-4-oxo-1,4-dihydro-3-pyridinecarboxylic acid derivatives for antimicrobial studies.

R. Johnstone et al., Aust. J. Chem., 11, 562 (1968) (Chem. Abs., 53,5310d (1968)) disclose 1-methyl-6-phenyl-4-pyridone-3-carboxylic acid asa decarboxylation product of a quinolone compound.

T. Kametani et al., J. Het. Chem., 14, 477 (1977) disclose the synthesisof various 1,4-dihydro-4-oxonicotinic acid derivatives, some of whichbear a 6-phenyl group, which compounds have antibacterial properties.

Wick et al., Ger. Offen. No. 2,901,868 (Chem. Abs., 91, 211273h (1979))disclose 4-pyridone-3-carboxylic acid derivatives, for example, the6-phenyl derivative thereof, which possess bactericidal and centralnervous system stimulant properties.

Adachi, Chem-Pharm. Bull., 17 (11), 2209 (1969), discloses ringconversion reactions of isoxazolium salts, two of the products of whichare ethyl 6-phenyl-1,2,5-trimethyl-4-pyridone-3-carboxylate and6-phenyl-1,2,5-trimethyl-4-pyridone-3-carboxylic acid. No biologicalactivity is disclosed.

Kigasawa et al., Japan Kokai 78 65,882 (Chem. Abs., 89, 129415f (1978)disclose several 1,4-dihydro-4-oxonicotinic acids having antibacterialactivity. Among the compounds disclosed are6-phenyl-5-methyl-1-ethyl-1,4-dihydro-4-oxonicotinic acid,6-methyl-5-phenyl-1-ethyl-1,4-dihydro-4-oxonicotinic acid, and5,6-diphenyl-1-ethyl-1,4-dihydro-4-oxonicotinic acid.

The present invention relates to N-alkyl-2-aryl-4-oxonicotinates,N-alkyl-5-aryl-4-oxonicotinates, N-alkyl-6-aryl-4-oxonicotinates andN-alkyl-2,6-diaryl-4-oxonicotinates and their use as plant hybridizationagents especially useful in wheat, barley and corn. These compounds areparticularly active as chemical gametocides and possess a high degree ofmale/female selectivity. Moreover, these compounds are relativelynoninjurious to both corn and wheat crops. The fact that these chemicalspossess a high degree of male sterility without affecting femalefertility makes them very useful as chemical gametocides.

SUMMARY OF THE INVENTION

This invention relates to compounds of the formula: ##STR7## wherein R₁is an optionally substituted (C₁ -C₆) alkyl or (C₂ -C₆) alkenyl group;at least one of R₂, R₅ and R₆ is ##STR8## wherein (1) when R₂ is##STR9## R₅ is a hydrogen atom, an alkyl group or a halogen atom and R₆is a hydrogen atom or an alkyl group,

(2) when R₅ is ##STR10## R₂ is an alkyl group and R₆ is a hydrogen atomor an alkyl group,

(3) when R₆ is ##STR11## R₂ is an optionally substituted (C₁ -C₆) alkylor (C₃ -C₆) alkenyl group and R₅ is a hydrogen atom, a (C₁ -C₆) alkylgroup or a halogen atom, and

(4) when R₂ and R₆ are both independently ##STR12## R₅ is a hydrogenatom or an alkyl group; Y is a hydrogen atom or an alkyl group; X is ahydrogen atom, a halogen atom, a trihalomethyl group, a (C₁ -C₆) alkylgroup, a nitro group, a cyano group or a (C₁ -C₆) alkoxy group; n is aninteger from 1 to 3; and the agronomically acceptable alkali metal oracid addition salts thereof. These compounds are useful as chemicalhybridization agents for monocotyledonous crops and are especiallyeffective in wheat, corn, barley, rice, rye, triticale, forage crops andthe like.

Those compounds which are highly potent chemical gametocides and whichproduce a high percentage of male sterility without affecting femalefertility of cereal grain and forage crops are especially useful aschemical hybridization agents according to the invention. As will beseen in the examples which follow, some of the compounds, particularlyat higher application rates, exhibit diminished female fertility alongwith high male sterility. The latter group of compounds nonetheless haveutility for producing new plant hybrids. Although some of the compoundsmay exhibit some phytotoxicity, the compounds are still useful for thepurpose of producing new plant hybrids. In addition to utility aschemical hybridization agents, the compounds of the invention are alsouseful as chemical gametocides in the agricultural production of ergot.

DETAILED DESCRIPTION OF THE INVENTION

The invention relates to N-alkyl-2-aryl-4-oxonicotinates,N-alkyl-5-aryl-4-oxonicotinates, N-alkyl-6-aryl-4-oxonicotinates, andN-alkyl-2,6-diaryl-4-oxonicotinates and their use as plant hybridizationagents in cereal grain and forage crops, especially in wheat, barley andcorn.

A. N-alkyl-2-aryl-4-oxonicotinates

In one preferred aspect, this invention relates to compounds of theformula: ##STR13##

By the term "optionally substituted alkyl or alkenyl group" as utilizedin the present specification and claims is meant a straight or branchedchain alkyl or alkenyl group which may be substituted with a hydroxygroup, a carboxy group, an aryl group or an aryl group substituted withup to two substituents selected from halogen, methyl, ethyl, methoxy,ethoxy, trifluoromethyl, nitro or cyano.

Since the compounds of the present invention possess both acidic andbasic functional groups, the term "agronomically acceptable salts" asutilized in the present specification and claims is meant to includesalts of the carboxyl group such as lithium, sodium, potassium, ammoniumand the like as well as acid addition salts such as hydrochloride,hydrobromide, sulfate, nitrate, perchlorate, acetate, oxalate and thelike.

Among the preferred compounds of the present invention are compounds ofGroup A, Formula (II) above, wherein R₁ is (C₁ -C₆) alkyl or allyl, R₅is hydrogen, (C₁ -C₃) alkyl or bromine, R₆ is (C₁ -C₆) alkyl, Y ishydrogen or a sodium or potassium cation, X is hydrogen or halogen, andn is the integer 1 or 2.

Among the more preferred compounds of the present invention arecompounds of Formula (II) wherein R₁ is (C₁ -C₃) alkyl, R₅ is hydrogen,R₆ is (C₁ -C₃) alkyl, Y is hydrogen or a sodium or potassium cation, Xis hydrogen, chlorine or fluorine and n is the integer 1 or 2.

Among the most preferred compounds of this invention are compounds ofFormula (I) wherein R₁ is a methyl or ethyl group; R₅ is a hydrogenatom; R₆ is a methyl group; and Y is a sodium or potassium cation andthe agronomically acceptable acid addition salts thereof.

Typical compounds encompassed by the present invention include:

1,6-dimethyl-2-phenyl-4-oxonicotinic acid

1-ethyl-6-methyl-2-phenyl-4-oxonicotinic acid

1,5,6-trimethyl-2-phenyl-4-oxonicotinic acid

1,6-diethyl-2-phenyl-4-oxonicotinic acid

6-ethyl-1-methyl-2-phenyl-4-oxonicotinic acid

1-methyl-2-phenyl-6-propyl-4-oxonicotinic acid

5-bromo-1,6-dimethyl-2-phenyl-4-oxonicotinic acid

1-allyl-6-methyl-2-phenyl-4-oxonicotinic acid

1,6-dimethyl-2-(4-chlorophenyl)-4-oxonicotinic acid

1-ethyl-6-methyl-2-(4-chlorophenyl)-4-oxonicotinic acid

1-ethyl-5,6-dimethyl-2-(4-chlorophenyl)-4-oxonicotinic acid

1,6-diethyl-2-(4-chlorophenyl)-4-oxonicotinic acid

6-ethyl-1-methyl-2-(4-chlorophenyl)-4-oxonicotinic acid

5-bromo-1-ethyl-6-methyl-2-(4-chlorophenyl)-4-oxonicotinic acid

1-allyl-6-methyl-2-(4-chlorophenyl)-4-oxonicotinic acid

6-methyl-2-(4-chlorophenyl)-1-propyl-4-oxonicotinic acid

1-butyl-6-methyl-2-(4-chlorophenyl)-4-oxonicotinic acid

1,6-dimethyl-2-(3-chlorophenyl)-4-oxonicotinic acid

1-ethyl-6-methyl-2-(3-chlorophenyl)-4-oxonicotinic acid

6-methyl-2-(3-chlorophenyl)-1-propyl-4-oxonicotinic acid

1-ethyl-5,6-dimethyl-2-(3-chlorophenyl)-4-oxonicotinic acid

5-chloro-1-ethyl-6-methyl-2-(3-chlorophenyl)-4-oxonicotinic acid

1-hexyl-6-methyl-2-(3-chlorophenyl)-4-oxonicotinic acid

1-allyl-6-ethyl-2-(3-chlorophenyl)-4-oxonicotinic acid

1,6-diethyl-2-(3-chlorophenyl)-4-oxonicotinic acid

1-ethyl-6-methyl-2-(4-trifluoromethylphenyl)-4-oxonicotinic acid

1-ethyl-6-methyl-2-(4-trifluoromethylphenyl)-4-oxonicotinic acid

1,6-dimethyl-2-(4-fluorophenyl)-4-oxonicotinic acid

1-ethyl-6-methyl-2-(4-fluorophenyl)-4-oxonicotinic acid

1-ethyl-6-methyl-2-(3-fluorophenyl)-4-oxonicotinic acid

1-ethyl-6-methyl-2-(4-bromophenyl)-4-oxonicotinic acid

1,6-dimethyl-2-(3,4-dichlorophenyl)-4-oxonicotinic acid

1-ethyl-6-methyl-2-(3,4-dichlorophenyl)-4-oxonicotinic acid

6-methyl-2-(3,4-dichlorophenyl)-1-propyl-4-oxonicotinic acid

6-methyl-1-pentyl-2-(3,4-dichlorophenyl)-4-oxonicotinic acid

6-ethyl-1-methyl-2-(3,4-dichlorophenyl)-4-oxonicotinic acid

1-ethyl-2-(3,4-dichlorophenyl)-6-propyl-4-oxonicotinic acid

1,5,6-trimethyl-2-(3,4-dichlorophenyl)-4-oxonicotinic acid

5-bromo-1,6-dimethyl-2-(3,4-dichlorophenyl)-4-oxonicotinic acid

1,5-diethyl-6-methyl-2-(3,4-dichlorophenyl)-4-oxonicotinic acid

5-ethyl-1,6-dimethyl-2-(3,4-dichlorophenyl)-4-oxonicotinic acid

1-ethyl-6-methyl-2-(2,4-dichlorophenyl)-4-oxonicotinic acid

1,6-dimethyl-2-(3,5-dichlorophenyl)-4-oxonicotinic acid

1-ethyl-6-methyl-2-(4-methylphenyl)-4-oxonicotinic acid

6-butyl-1-methyl-2-(4-methylphenyl)-4-oxonicotinic acid

and the agronomically acceptable salts thereof.

The compounds of Group A of the present invention can be prepared byvarious synthetic routes found in the art. In particular, the compoundsof the present invention can be prepared by the reaction of a suitablysubstituted 4-hydroxy-2-pyrone of the formula: ##STR14## wherein R⁶ isas defined above with a benzoylhalide of the formula: ##STR15## whereinX is as defined above in the presence of an acid scavenger such aspyridine, triethylamine and the like, at temperatures from about 0° toabout 10° C. to form a 4-benzoyloxy-2-pyrone of the formula: ##STR16##wherein R₆ and X and n are as defined above.

This reaction is discussed in E. Marcus, J. F. Stephen, J. K. Chan,Journal of Heterocyclic Chemistry, p. 13, 1966. This benzoate canundergo a Fries-type rearrangement with anhydrous aluminum chloride atelevated temperatures to give the product of the formula: ##STR17## asdiscussed in the E. Marcus, et al. reference, ibid. The benzoylpyrone ofthe formula (VI) above can then be reacted with a suitable alcohol (ROH)in the presence of a similarly substituted trialkylorthoformate (RO)₃ CHutilizing an acid catalyst selected from the group consisting ofsulfuric, hydrochloric, trifluoroacetic, acetic, hydrobromic, and thelike, at temperatures from about 0° to about 200° C. to form the3-carboxy-4-pyrone of the formula: ##STR18## The 3-carboxy-4-pyroneesters of formula (VII) can be reacted with any suitably substitutedamine of the formula:

    R.sub.1 --NH.sub.2                                         (VIII)

to yield a 1-alkyl-2-aryl-4-oxonicotinate ester of formula (IX) where R₅is hydrogen. ##STR19## This reaction is generally carried out in aninert solvent, such as toluene, xylene, benzene, chloroform, methylenechloride, methanol, ethanol or the like, at room temperature or at atemperature at which the water formed during the reaction can be removedby azeotropic distillation, using about 0 to 5% by weight of an acidcatalyst such as p-toluenesulfonic acid, hydrochloric acid, sulfuricacid, methanesulfonic acid, or the like. The free acid, its salts,amides, and other esters can then be prepared by conventionaltechniques.

The reaction of 3-carboxy-4-pyrone ester of formula (VII) with excessamine of formula (VIII) in methanol or ethanol at 0°-50° C. also resultsin the formation of a 2:1 amine:pyrone adduct of formula (X). ##STR20##Compound (X) can be converted to (IX) by hydrolysis with dilute aqueousacids such as hydrochloric, sulfuric, trifluoracetic or methanesulfonicat 0°-50° C. Alternately, 2:1 adduct (X) can be alkylated with an alkylhalide in an inert solvent such as methylene chloride, benzene,tetrahydrofuran, diethyl ether and the like to provide a material offormula (XI) wherein R₅ is an alkyl group; ##STR21##

This compound can be hydrolyzed in aqueous acids at 0°-50° C. asdescribed above to yield the corresponding1,5-dialkyl-2-aryl-4-oxonicotinate ester of formula (IX) where R₅ isalkyl. The oxonicotinic acid esters produced in the above reactions canbe converted to the free acids by hydrolysis with a strong base such assodium hydroxide or potassium hydroxide and the like followed byneutralization with a strong acid.

Another route to the preparation of the compounds according to Formula(II) wherein R₁ and X are as defined above, R₅ is hydrogen and R₆ ismethyl is depicted in the following reaction sequence: ##STR22## whereinY is a (C₁ -C₆) alkyl group. ##STR23## wherein Y is a (C₁ -C₆) alkylgroup. ##STR24## In the above reaction sequence the solvents for Eq. (1)can be selected from methanol, ethanol, water and the like and thereaction is run at temperatures from about 20° to about 100° C. In Eq.(2), the inert solvent is selected from ethers, methylene chloride,aromatic hydrocarbons, acetone, acetonitrile and the like and thereaction is run at temperatures from about 10° to about 150° C. In Eq.(3) the saponification reaction is run at 10°-100° C. with a strongbase, such as sodium or potassium hydroxide, and the alkali salt isconverted to the free acid via mineral acids such as hydrochloride,sulfuric and the like.

Another route to the compounds of the present invention wherein R₁ andR₆ are as defined above and R₅ is hydrogen or alkyl is shown in equation(4) below. ##STR25## wherein Y is an alkyl group.

In the reaction sequence of Eq. (4) the reaction can be run either neator in an inert cosolvent optionally in the presence of an acid catalystsuch as toluene sulfonic acid, sulfuric acid, acetic acid and the likeat temperatures from about 100° C. to about 300° C.

A route to the 5-halo compounds encompassed by the present invention isshown in Eq. (5) below. ##STR26## In this reaction sequence any proticsolvent such as water, methanol, ethanol and the like can be utilized asthe reaction medium and the reaction can be carried out at temperaturesfrom about 10° to about 50° C.

The salts of the oxonicotinic acids of the present invention can beprepared by generally known procedures such as dissolving the acids in aprotic solvent such as methanol, ethanol, water and the like andtreating them with an equivalent amount of a strong base such as sodiumor potassium hydroxide and the like, and recovering the salt either bystripping off the solvent or precipitating the solid out with adiethylether, hexane, benzene and the like.

Table I below is presented to illustrate the more preferred compounds ofthe present invention. This table and Tables II and III in which theanalytical data is presented for these compounds are not to beinterpreted in any way as being limits on the breadth and scope of thepresent invention:

                  TABLE I                                                         ______________________________________                                         ##STR27##                                                                    Ex-                                                                           am-                                                                           ple                                                                           #    X.sub.(n)                                                                              R.sub.1     R.sub.5                                                                            R.sub.6                                                                              Y                                       ______________________________________                                        1    H        CH.sub.3    H    CH.sub.3                                                                             CH.sub.3                                2    H        CH.sub.3    H    CH.sub.3                                                                             CH.sub.2 CH.sub.3                       3    H        CH.sub.3    H    CH.sub.3                                                                             CH.sub.2 CH.sub.3.HCl                   4    H        CH.sub.3    H    CH.sub.3                                                                             H                                        4a  H        CH.sub.3    H    CH.sub.3                                                                             Na                                      5    H        CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             H                                       6    H        n-C.sub.3 H.sub.7                                                                         H    CH.sub.3                                                                             H                                        6a  H        n-C.sub.3 H.sub.7                                                                         H    CH.sub.3                                                                             Na                                      7    H        n-C.sub.4 H.sub.9                                                                         H    CH.sub.3                                                                             H                                        7a  H        n-C.sub.4 H.sub.9                                                                         H    CH.sub.3                                                                             Na                                      8    H        CH.sub.3    H    CH.sub.2 CH.sub.3                                                                    H                                        8a  H        CH.sub.3    H    CH.sub.2 CH.sub.3                                                                    Na                                      9    H        CH.sub.3    H    n-C.sub.3 H.sub.7                                                                    H                                        9a  H        CH.sub.3    H    n-C.sub.3 H.sub.7                                                                    Na                                      10   H        CH.sub.2 CH.sub.3                                                                         H    CH.sub.2 CH.sub.3                                                                    H                                       10a  H        CH.sub.2 CH.sub.3                                                                         H    CH.sub.2 CH.sub.3                                                                    Na                                      11   H        CH.sub.3    CH.sub.3                                                                           CH.sub.3                                                                             H                                       11a  H        CH.sub.3    CH.sub.3                                                                           CH.sub.3                                                                             Na                                      12   4-Cl     H           H    CH.sub.3                                                                             H                                       12a  4-Cl     H           H    CH.sub.3                                                                             Na                                      13   4-Cl     CH.sub.3    H    CH.sub.3                                                                             H                                       13a  4-Cl     CH.sub.3    H    CH.sub.3                                                                             Na                                      14   4-Cl     CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             CH.sub.3                                15   4-Cl     CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             CH.sub.2 CH.sub.3                       16   4-Cl     CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             H                                       16a  4-Cl     CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             Na                                      17   4-Cl     CH.sub.2 CH.sub.3                                                                         CH.sub.3                                                                           CH.sub.3                                                                             H                                       17a  4-Cl     CH.sub.2 CH.sub.3                                                                         CH.sub.3                                                                           CH.sub.3                                                                             Na                                      18   4-Cl     n-C.sub.3 H.sub.7                                                                         H    CH.sub.3                                                                             H                                       18a  4-Cl     n-C.sub.3 H.sub.7                                                                         H    CH.sub.3                                                                             Na                                      19   4-Cl     CH.sub.2 CH.sub.2 OH                                                                      H    CH.sub.3                                                                             H                                       19a  4-Cl     CH.sub.2 CH.sub.2 OH                                                                      H    CH.sub.3                                                                             Na                                      20   4-Cl     CH.sub.2 CO.sub.2 H                                                                       H    CH.sub.3                                                                             CH.sub.3                                20a  4-Cl     CH.sub.2 CO.sub.2 Na                                                                      H    CH.sub.3                                                                             CH.sub.3                                21   4-Cl     CH.sub.2 CO.sub.2 H                                                                       H    CH.sub.3                                                                             H                                       21a  4-Cl     CH.sub.2 CO.sub.2 Na                                                                      H    CH.sub.3                                                                             Na                                      22   4-Cl     CH.sub.2 CHCH.sub.2                                                                       H    CH.sub.3                                                                             H                                       22a  4-Cl     CH.sub.2 CHCH.sub.2                                                                       H    CH.sub.3                                                                             Na                                      23   4-Cl     n-C.sub.6 H.sub.13                                                                        H    CH.sub.3                                                                             H                                       23a  4-Cl     n-C.sub.6 H.sub.13                                                                        H    CH.sub.3                                                                             Na                                      24   4-Cl     CH.sub.2 CH.sub.2 Ph                                                                      H    CH.sub.3                                                                             H                                       24a  4-Cl     CH.sub.2 CH.sub.2 Ph                                                                      H    CH.sub.3                                                                             Na                                      25   4-CH.sub.3                                                                             CH.sub.3    H    CH.sub.3                                                                             H                                       25a  4-CH.sub.3                                                                             CH.sub.3    H    CH.sub.3                                                                             Na                                      26   4-CH.sub.3                                                                             CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             H                                       26a  4-CH.sub.3                                                                             CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             Na                                      27   4-F      CH.sub.3    H    CH.sub.3                                                                             H                                       27a  4-F      CH.sub.3    H    CH.sub.3                                                                             Na                                      28   4-F      CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             H                                       28a  4-F      CH.sub. 2 CH.sub.3                                                                        H    CH.sub.3                                                                             Na                                      29   4-F      n-C.sub.3 H.sub.7                                                                         H    CH.sub.3                                                                             H                                       29a  4-F      n-C.sub.3 H.sub.7                                                                         H    CH.sub.3                                                                             Na                                      30   3-Cl     CH.sub.3    H    CH.sub.3                                                                             H                                       30a  3-Cl     CH.sub.3    H    CH.sub.3                                                                             Na                                      31   3-Cl     CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             CH.sub.3                                32   3-Cl     CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             H                                       32a  3-Cl     CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             Na                                      33   3-Cl     n-C.sub.3 H.sub.7                                                                         H    CH.sub.3                                                                             H                                       33a  3-Cl     n-C.sub.3 H.sub.7                                                                         H    CH.sub.3                                                                             Na                                      34   3-Cl     n-C.sub.4 H.sub.9                                                                         H    CH.sub.3                                                                             H                                       34a  3-Cl     n-C.sub.4 H.sub.9                                                                         H    CH.sub.3                                                                             Na                                      35   3-Cl     CH.sub.2 Ph H    CH.sub.3                                                                             H                                       35a  3-Cl     CH.sub.2 Ph H    CH.sub.3                                                                             Na                                      36   3-CH.sub.3                                                                             CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             H                                       36a  3-CH.sub.3                                                                             CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             Na                                      37   3-F      CH.sub.3    H    CH.sub.3                                                                             H                                       37a  3-F      CH.sub.3    H    CH.sub.3                                                                             Na                                      38   3-F      CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             H                                       38a  3-F      CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             Na                                      39   2-Cl     CH.sub.3    H    CH.sub.3                                                                             H                                       39a  2-Cl     CH.sub.3    H    CH.sub.3                                                                             Na                                      40   2-Cl     CH.sub.3    H    CH.sub.3                                                                             H                                       40a  2-Cl     CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             Na                                      41   3,4-diCl H           H    CH.sub.3                                                                             CH.sub.3                                42   3,4-diCl CH.sub.3    H    CH.sub.3                                                                             H                                       42a  3,4-diCl CH.sub.3    H    CH.sub.3                                                                             Na                                      43   3,4-diCl CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             H                                       43a  3,4-diCl CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             Na                                      44   3,4-diCl n-C.sub.3 H.sub.7                                                                         H    CH.sub.3                                                                             H                                       44a  3,4-diCl n-C.sub.3 H.sub.7                                                                         H    CH.sub.3                                                                             Na                                      45   2,4-diCl CH.sub.3    H    CH.sub.3                                                                             H                                       45a  2,4-diCl CH.sub.3    H    CH.sub.3                                                                             Na                                      46   2,4-diCl CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             H                                       46a  2,4-diCl CH.sub.2 CH.sub.3                                                                         H    CH.sub.3                                                                             Na                                      47   H        CH.sub.3    Br   CH.sub.3                                                                             H                                       47a  H        CH.sub.3    Br   CH.sub.3                                                                             Na                                      ______________________________________                                    

                  TABLE II                                                        ______________________________________                                        Example # mp (°C.)                                                                          % C    % H    % N  % X                                   ______________________________________                                         1        226-8      70.02  5.88   5.45 --                                                         70.35  6.01   3.60 --                                     2        244-8      70.83  6.32   5.16 --                                                         70.92  6.17   5.66 --                                     3         229-32    62.44  5.89   4.55 --                                                         62.00  5.67   4.78 --                                     4        246-8      69.12  5.39   5.76 --                                                         69.05  5.66   5.80 --                                     4a       .sup.a     --     --     --   --                                     5        252-4      70.02  5.88   5.45 --                                                         69.63  5.76   5.64 --                                     5a       .sup.a     --     --     --   --                                     6        210-2      70.83  6.32   5.16 --                                                         70.67  5.93   5.33 --                                     6a                                                                            7        165-7      71.56  6.71   4.91 --                                                         73.87  6.80   5.30 --                                     7a       .sup.a     --     --     --   --                                     8        244-5      70.02  5.88   5.44 --                                                         70.15  5.65   6.07 --                                     8a       .sup.a     --     --     --   --                                     9        126-8      70.83  6.32   5.16 --                                                         70.61  6.39   5.36 --                                     9a       .sup.a     --     --     --   --                                    10        187-8      70.83  6.32   5.16 --                                                         70.87  6.29   5.66 --                                     10a      .sup.a     --     --     --   --                                    11        210-4      70.02  5.88   5.44 --                                                         69.92  5.96   5.96 --                                     11a                                                                          12        250-1      59.31  3.82   5.31 13.45                                                      59.05  3.77   5.38 13.46                                  12a      .sup.a     --     --     --   --                                    13        242-4      60.55  4.36   5.04 12.77                                                      60.17  4.36   5.53 13.07                                  13a      .sup.a     --     --     --   --                                    14        217-9      62.85  5.28   4.58 11.60                                                      62.98  5.49   4.55 11.45                                 15                                                                            16        235-7      61.75  4.84   4.80 12.16                                                      60.50  4.75   5.75 13.66                                  16a      .sup.a     --     --     --   --                                    17        240-2      62.85  5.28   4.58 11.60                                                      62.86  5.37   4.71 11.48                                  17a      .sup.a     --     --     --   --                                    18        213-6      62.85  5.27   4.58 11.60                                                      62.76  5.25   5.05 11.50                                  18a      .sup.a     --     --     --   --                                    19         217-20    58.54  4.59   4.55 11.52                                                      58.31  4.52   4.75 11.91                                  19a      .sup.a     --     --     --   --                                    20        224        57.24  4.20   4.17 10.57                                                      57.21  4.20   4.66 10.30                                  20a      .sup.a     --     --     --   --                                    21         158-62    50.36  4.51   3.92  9.91                                 (dihydrate)          50.38  3.93   3.89  9.85                                  21a      .sup.a     --     --     --   --                                    22         219-21    63.26  4.65   4.61 11.67                                                      63.30  4.59   5.09 11.75                                  22a      .sup.a     --     --     --   --                                    23        178-9      65.60  6.38   4.03 10.19                                                      65.84  6.66   4.29 10.22                                  23a      .sup.a     --     --     --   --                                    24        265        68.57  4.93   3.81  9.64                                                      68.48  4.95   4.12  9.44                                  24a      .sup.a     --     --     --   --                                    25        250        70.02  5.88   5.44 --                                                         69.92  6.03   5.46 --                                     25a      .sup.a     --     --     --   --                                    26        248-9      70.83  6.31   5.16 --                                                         70.64  6.39   5.60 --                                     26a      .sup.a     --     --     --   --                                    27        263-5      64.36  4.63   5.36  7.27                                                      64.60  4.63   5.53  7.10                                  27a      .sup.a     --     --     --   --                                    28        258-60     65.44  5.13   5.09  6.90                                                      65.60  5.26   5.24  6.80                                  28a      .sup.a     --     --     --   --                                    29        225-6      66.42  5.58   4.84  6.57                                                      66.60  5.74   5.11  6.47                                  29a      .sup.a     --     --     --   --                                    30        248-50     60.55  4.36   5.04 12.77                                                      60.68  4.47   5.41 12.77                                  30a      .sup.a     --     --     --   --                                    31        173-5      62.85  5.28   4.58 11.60                                                      62.88  5.54   5.06 11.80                                 32        241-4      61.75  4.84   4.80 12.16                                                      62.01  4.83   4.97 12.25                                  32a      .sup.a     --     --     --   --                                    33        164-9      62.85  5.28   4.58 11.60                                                      60.83  5.40   4.34 14.09                                  33a      .sup.a     --     --     --   --                                    34        174-6      63.85  5.67   4.38 11.09                                                      63.65  5.86   4.41 11.19                                  34a      .sup.a     --     --     --   --                                    35        235-5      67.89  4.56   3.96 10.02                                                      68.14  4.54   4.06 10.18                                  35a      .sup.a     --     --     --   --                                    36        183        70.83  6.31   5.16 --                                                         70.29  6.38   5.24 --                                     36a      .sup.a     --     --     --   --                                    37        243-4      64.36  4.63   5.36  7.27                                                      64.34  4.96   5.40  7.07                                  37a      .sup.a     --     --     --   --                                    38        226-7      65.44  5.13   5.09  6.90                                                      65.43  5.24   5.10  6.93                                  38a      .sup.a     --     --     --   --                                    39        221-3      60.55  4.36   5.04 12.77                                                      60.53  4.30   4.95 17.62                                 40        212-5      61.75  4.84   4.80 12.16                                                      61.94  4.85   4.93 12.06                                  40a      .sup.a     --     --     --   --                                    41        245-9      53.87  3.55   4.49 22.72                                                      53.79  3.57   4.95 23.09                                 42        246-9      53.87  3.55   4.49 22.72                                                      53.40  3.55   4.42 23.10                                  42a      .sup.a     --     --     --   --                                    43        238-9      55.23  4.02   4.30 21.74                                                      54.68  3.90   4.06 23.06                                  43a      .sup.a     --     --     --   --                                    44        232-3      56.48  4.44   4.19 20.84                                                      56.69  4.47   4.29 20.49                                  44a      .sup.a     --     --     --   --                                    45        232-4      53.87  3.55   4.49 27.72                                                      53.96  3.57   4.88 22.69                                  45a      .sup.a     --     --     --   --                                    46        195        55.23  4.02   4.30 21.72                                                      55.82  4.02   4.72 21.73                                  46a      .sup.a     --     --     --   --                                    47        252-3      52.19  3.76   4.35 24.81                                                      51.72  3.67   4.26 24.78                                  47a      .sup.a     --     --     --   --                                    ______________________________________                                         .sup.a no melting point taken. Too glassy.                               

                  TABLE III                                                       ______________________________________                                        NMR DATA                                                                      Ex-                                                                           am-                                                                           ple  Solvent   NMR--CHEMICAL SHIFT*                                           ______________________________________                                         1   CDCl.sub.3                                                                              3H at 2.4 ppm(s); 3H at 3.3 ppm(s); 3H at 3.45                                (s); 1H at 6.4 ppm(s); 5H at 7.5 ppm(m)                         2   --        --                                                              3   --        --                                                              4   CF.sub.3 CO.sub.2 H                                                                     3H at 2.9 ppm(s); 3H at 3.8 ppm(s); 6H at                                     7.6 ppm(m)                                                      4a  --        --                                                              5   CF.sub.3 CO.sub.2 H                                                                     3H at 1.4 ppm(t); 3H at 2.9 ppm(s); 2H at                                     4.5 ppm(q); 6H at 7.7 ppm(m)                                    6   --        --                                                              6a  --        --                                                              7   CDCl.sub.3                                                                              7H at 0.7-17 ppm(m); 3H at 2.5 ppm(s); 2H at                                  3.7 ppm(m); 1H at 6.8 ppm(s); 5H at 7.5                                       ppm(m)                                                          7a  --        --                                                              8a  --        --                                                              9   --        --                                                              9a  --        --                                                             10   --        --                                                             10a  --        --                                                             11   --        --                                                             11a  --        --                                                             12   CF.sub.3 CO.sub.2 H                                                                     3H at 2.9 ppm(s); 5H at 7.6 ppm(m)                             12a  --        --                                                             13   CDCl.sub.3 +                                                                            3H at 2.5 ppm(s); 3H at 3.3 ppm(s); 1H at                           dmso-d.sub.6                                                                            6.8 ppm(s); 4H at 7.5 ppm(q)                                   13a  --        --                                                             14   CDCl.sub.3                                                                              3H at 1.1 ppm(t); 3H at 2.4 ppm(s); 3H at                                     3.5 ppm(s); 2H at 3.8 ppm(q), 1H at 6.5 ppm(s)                                4H at 7.5 ppm(q)                                               15   --        --                                                             16   CDCl.sub.3                                                                              3H at 1.2 ppm(t); 3H at 2.75 ppm(s); 2H at                                    4.2 ppm(q); 1H at 6.9 ppm(s); 4H at 7.9                                       ppm(m)                                                         16a  D.sub.2 O 3H at 0.8 ppm(t); 3H at 2.3 ppm(s); 2H at                                     3.7 ppm(q); 1H at 6.6 ppm(s), 4H at 7.6 ppm(s)                 17   DMSO--d.sub.6                                                                           3H at 1.1 ppm(t); 3H at 2.2 ppm(s); 3H at 2.6                                 ppm(s); 2H at 3.9 ppm(q); 4H at 7.6 ppm(q)                     17a  --        --                                                             18   --        --                                                             18a  --        --                                                             19   DMSO--d.sub.6                                                                           3H at 2.6 ppm(s); 2H at 3.4 ppm(m); 2H at 3.9                                 ppm(m); 1H at 6.9 ppm(s); 4H at 7.4 ppm(q)                     19a  --        --                                                             20   DMSO--d.sub.6                                                                           3H at 2.3 ppm(s); 3H at 3.4 ppm(s); 2H at 4.5                                 ppm(s); 1H at 6.4 ppm(s); 4H at 7.6 ppm(q)                     20a  --        --                                                             21   --        --                                                             21a  --        --                                                             22   --        --                                                             22a  --        --                                                             23   --        --                                                             23a  --        --                                                             24   --        --                                                             24a  --        --                                                             25   CDCl.sub.3 +                                                                            3H at 2.4 ppm(s); 3H at 2.5 ppm(s); 3H at 3.3                       dmso-d.sub.6                                                                            ppm(s); 1H at 6.8 ppm(s); 4H at 7.3 ppm(q)                     25a  --        --                                                             26   --        --                                                             26a  --        --                                                             27   CF.sub.3 CO.sub.2 H                                                                     3H at 2.8 ppm(s); 3H at 3.8 ppm(s); 5H at 7.5                                 ppm(m)                                                         27a  --        --                                                             28   --        --                                                             28a  --        --                                                             29   --        --                                                             29a  --        --                                                             30   --        --                                                             30a  --        --                                                             31   CDCl.sub.3                                                                              3H at 1.1 ppm(t); 3H at 2.4 ppm(s); 3H at 3.5                                 ppm(s); 2H at 3.8 ppm(q); 1H at 6.4 ppm(s);                                   4H at 7.5 ppm(m)                                               32   --        --                                                             32a  --        --                                                             33   CDCl.sub.3                                                                              3H at 0.7 ppm(t); 2H at 1.5 ppm(m); 3H at 2.6                                 ppm(s); 2H at 3.6 ppm(q); 1H at 6.8 ppm(s);                                   4H at 7.5 ppm(m)                                               33a  --        --                                                             34   CDCl.sub.3                                                                              7H at 0.7-1.7 ppm(m); 3H at 2.5 ppm(s); 2H at                                 3.7 ppm(m); 1H at 6.8 ppm(s); 4H at 7.5                                       ppm(m)                                                         34a  --        --                                                             35   --        --                                                             35a  --        --                                                             36   CDCl.sub.3                                                                              3H at 1.1 ppm(t); 3H at 2.4 ppm(S); 3H at 2.6                                 ppm(s); 2H at 3.9 ppm(q); 1H at 6.8 ppm(s);                                   4H at 7.4 ppm(m)                                               36a  --        --                                                             37   --        --                                                             37a  --        --                                                             38   DMSO--d.sub.6                                                                           3H ar 1.1 ppm(t); 3H at 2.6 ppm(s); 2H at 3.8                                 ppm(q); 1H at 6.9 ppm(s); 4H at 7.5 ppm(m)                     38a  --        --                                                             39   --        --                                                             39a  --        --                                                             40   --        --                                                             40a  --        --                                                             41   CF.sub.3 CO.sub.2 H                                                                     3H at 2.8 ppm(s); 3H at 3.9 ppm(s); 4H at 7.6                                 ppm(m)                                                         42   --        --                                                             42a  --        --                                                             43   --        --                                                             43a  --        --                                                             44   --        --                                                             44a  --        --                                                             45   CF.sub.3 CO.sub.2 H                                                                     3H at 2.9 ppm(s); 3H at 3.9 ppm(s); 4H at 7.7                                 ppm(m)                                                         45a  --        --                                                             46   CDCl.sub.3                                                                              3H at 1.2 ppm(t); 3H at 2.6 ppm(s); 2H at 3.8                                 ppm(q); 1H at 6.8 ppm(s); 3H at 7.5 ppm(m)                     46a  --        --                                                             47   --        --                                                             47a  --        --                                                             ______________________________________                                         *s = singlet                                                                  t = triplet                                                                   q = quartet                                                                   m = multiplet                                                            

The following examples are presented to illustrate the methods forpreparation of the compounds of the present invention. Again theseexamples are not to be interpreted as being limits upon the breadth andscope of the present invention.

EXPERIMENTAL Example #1

Part a

A flask fitted with a reflux condenser and calcium chloride drying tubeis charged with 70 ml dry methanol, 7.3 g of 96% sulfuric acid and 10.15g of trimethyl orthoformate. 3-Benzoyl-4-hydroxy-6-methyl-2-pyrone (22g) is then added in small portions and the resulting reaction mixture isrefluxed for 24 hours. The mixture is cooled and poured into water.Extraction with methylene chloride yields 17.7 g of crude3-methoxycarbonyl-6-methyl-2-phenyl-4-pyrone. mp (from methylenechloride/ether)=101°-102.5° C.

Part b

3.8 g of 3-methoxycarbonyl-6-methyl-2-phenyl-4-pyrone, 33.3 ml ofmethanol, 13.3 ml of 40% aqueous methylamine and 2 ml of glacial aceticacid are mixed in a stoppered flask at room temperature and stored for18 hours. The reaction mixture is then poured into approximately 100 mlof water and the pH is adjusted to 5 (addition of dilute HCl).Extraction with methylene chloride (3×50 mls) and evaporation of theorganic siolvent yields 3.0 g of methyl1,6-dimethyl-2-phenyl-4-oxonicotinate as a crystalline solid. mp(methylene chloride/ether)=226°-228° C.

Example #2

10.25 g of ethyl beta-methylaminocinnamate, 9.4 g of technical gradediketene and 25 ml dry methylene chloride are mixed in a flask fittedwith a calcium chloride drying tube. The reaction mixture is stored atroom temperature for 117 hours. Approximately 75 ml of dry ether isadded and the resulting crystalline solid is filtered to yield 8.5 g ofethyl 1,6-dimethyl-2-phenyl-4-oxonicotinate. mp (toluene)=244°-248° C.

Example #4

6.0 gms of crude methyl 1,6-dimethyl-2-phenyl-4-oxonicotinate issuspended in 66 g of 5% aqueous sodium hydroxide solution. The reactionmixture is heated on a steambath (85°) for two hours. The resultinghomogeneous solution is cooled and acidified with dilute HCl. Theresulting solid is collected by filtration yielding 4.9 g of1,6-dimethyl-2-phenyl-4-oxonicotinic acid. mp (acetonitrile/methylenechloride)=246°-249° C. (dec.).

Example 4a

1.69 g of 1,6-dimethyl-2-phenyl-4-oxonicotinic acid is suspended inapproximately 50 ml of methanol. NaOH pellets (0.305 gms) are added withstirring. After both the acid and the sodium hydroxide dissolve thesolution is evaporated to dryness in vacuo. Sodium1,6-dimethyl-2-phenyl-4-oxonicotinate is then isolated as a glossy,somewhat hydroscopic solid. Yield=1.6 g.

Example 8

Part a:

12 g of ethyl beta-methylaminocinnamate, 18 g of ethyl propionylacetateand 100 mg of toluenesulfonic acid monohydrate are added to a 50 ml3-neck flask fitted with a nitrogen inlet, magnetic stirring bar,thermometer and a short-path distillation head (with receiver). Thereaction mixture is heated to 170°-175° C. under a slow stream of drynitrogen. Ethanol and water are collected in the distillation receiver.After four hours the reaction mixture is cooled and poured into a largevolume of ether (150 ml). A pink solid forms which is collected byfiltration to yield 4.1 g of ethyl6-ethyl-1-methyl-2-phenyl-4-oxonicotinate. mp (EtOAc)=210°-212° C.

Part b:

2.2 g of ethyl 6-ethyl-1-methyl-2-phenyl-4-oxonicotinate is suspended in35 ml of 5% aqueous sodium hydroxide solution. The resulting suspensionis heated on a steambath for 4 hours, cooled and acidified with diluteHCl to yield 2.0 g of 6-ethyl-1-methyl-2-phenyl-4-oxonicotinic acid. mp(CH₃ CN)=244°-245° C.

Example 11

Part a:

12.0 g of ethyl beta-methylaminocinnamate, 18 g of ethyl2-methylacetoacetate and 100 mg toluenesulfonic acid monohydrate ismixed in a 50 ml 3-neck flask filled with a nitrogen inlet, magneticstirring bar, thermometer and a short-path distillation head (withreceiver). The reaction mixture is heated (170°-175° C.) for seven hoursunder a gentle stream of nitrogen. Ethanol and water are collected inthe distillation receiver. The reaction mixture is cooled and pouredinto 100 ml of dry ether. Ethyl 1,5,6-trimethyl-2-phenyl-4-oxonicotinateforms as a brownish precipitate. Yield=1.03 g.

Part b:

1.03 g of crude ethyl 1,5,6-trimethyl-2-phenyl-4-oxonicotinate issuspended in 20 ml of warm (85°) 5% aqueous NaOH solution for 4 hours.Acidification with dilute hydrochloric acid yields 0.8 g of1,5,6-trimethyl-2-phenyl-4-oxonicotinate mp (CH₃ CN)=210°-214° C.

Example 14

Part a

A 5000 ml 3-neck flask is fitted with a N₂ inlet, magnetic stirring bar,thermometer and a Dean-Stark trap with condenser. 2300 ml of drymethanol is added to the flask along with 244 g of 96% H₂ SO₄ and 352 gof trimethyl orthoformate. 173 g of3-(4'-chlorobenzoyl)-4-hydroxy-6-methyl-2-pyrone is added and thereaction mixture is gently brought to reflux. The most volatileby-product of the reaction (methyl formate) is condensed and collectedin the Dean-Stark trap. After 28-281/2 hours of reflux the reactionmixture is cooled to room temperature and poured into 6000 ml of brine.The resulting suspension is extracted with methylene chloride (6×250ml). Evaporation of the solvent yields 153 g of3-methoxycarbonyl-6-methyl-2-(4'-chlorophenyl)-4-pyrone. mp (methylenechloride/ether)=131°-132° C.

Part b:

A 1000 ml flask is fitted with a magnetic stirring bar and a sidearmaddition funnel. 500 ml of methanol, 30 ml of glacial acetic acid and 60g of 3-methoxycarbonyl-6-methyl-2-(4'-chlorophenyl)-4-pyrone are added.120 mls of 70% aqueous ethylamine is placed in the addition funnel andadded very slowly (4 hr. addition time). 50 ml of water is then addedfollowed by 100 ml of concentrated HCl (cooling required). The reactionmixture is allowed to stand undisturbed for 30 minutes. The bulk of themethanol is then removed in vacuo leaving 46.1 g of methyl1-ethyl-6-methyl-2-(4'-chlorophenyl)(-4-osonicotinate. mp (methylenecnhloride/ether)=217°-219° C.

Example 16

46.1 g of crude methyl1-ethyl-6-methyl-2-(4'-chlorophenyl)-4-oxonicotinate is suspended in 600ml of 5% aqueous NaOH solution and warmed to 80°-85°. After 1-11/2 hoursat this temperature the reaction mixture is cooled and acidified withdilute HCl. The resulting solid precipitate is collected by filtration,yielding 42 g of 1-ethyl-6-methyl-2-(4'-chlorophenyl)-4-oxonicotinicacid, mp (methylene chloride/ether)=235°-237° C.

Example 15

4.64 g of ethyl beta-ethylamino-4-chlorocinnamate, 4.61 g of technicalgrade diketene and 15 ml of methylene chloride are mixed in a flaskfitted with a calcium chloride drying tube. The mixture is maintained atroom temperature for 137 hours. The methylene chloride is removed invacuo and the residue triturated with ether to yield 3.2 g of crudeethyl 1-ethyl-6-methyl-2-(4'-chlorophenyl)-4-oxonicotinate. mp(215°-217° C.).

Example 15

6 g of ethyl beta-ethylamino-4-chlorocinnamate and 12 g of ethylacetoacetate is mixed in a 50 ml 3-neck flask fitted with a N₂ -inlet,magnetic stirring bar, thermometer and a short-path distillation head(with receiver). The reaction mixture is heated (170° C.) for 10 hours.Ethanol and water is collected in the distillation receiver. Thereaction mixture are cooled and triturated with ethyl acetate/ether toyield 2.52 g of ethyl1-ethyl-6-methyl-2-(4'-chlorophenyl)-4-oxonicotinate.

Example 17

Part a

69 g of 3-methoxycarbonyl-6-methyl-2-(4'-chlorophenyl)-4-pyrone, 500 mlof methanol, 90 ml of water and 30 mls of glacial acetic acid are mixedin a 1000 ml flask fitted with a magnetic stirring bar and a sidearmaddition funnel. 120 ml of 70% aqueous ethylamine is added over thecourse of one hour. The reaction mixture is then allowed to stand atroom temperature for one hour, neutralized with dilute HCl and extractedwith methylene chloride (2×250 ml, 2×150 ml). The organic extracts areevaporated and the residue triturated with ether. The first crop ofcrystals is pure methyl1-ethyl-6-methyl-2-(4'-chlorophenyl)-4-oxonicotinate (33.1 g). The solidthat forms upon further concentration of the mother liquor is purealpha-[3-ethylamino-2-butenoyl]-beta-ethylamino-4-chlorocinnamate.Yield=11 g and mp=144° C. (ether).

Part b

7 g ofalpha-[3-ethylamino-2-butenoyl]-beta-ethylamino-4-chlorocinnamate, 5.7 gmethyl iodide, and 20 ml of methylene chloride are mixed in a sealedflask, and stored for 22 hours at room temperature. The contents of theflask are then poured into a separatory funnel and washed with water.Evaporation of the organic layer leaves 9.4 g of oil which is dissolvedin 80 ml of tetrahydrofuran. 60 ml of water and 4 ml of trifluoroaceticacid is then added and the mixture is allowed to remain at roomtemperature for two hours. Subsequent dilution with water and extractionwith methylene chloride provides 8.0 g of crude 4-oxonicotinate ester.This material is then heated in 80 ml of 5% aqueous sodium hydroxidesolution (85° C., 2 hrs.) and acidified to yield 2.3 g of1-ethyl-5,6-dimethyl-2-(4'-chlorophenyl)-4-oxonicotinic acid.mp=240°-242° C. (acetonitrile).

Example 20

8.7 g of 3-methoxycarbonyl-6-methyl-2-(4'-chlorophenyl)-4-pyrone issuspended in 100 ml of methanol and 10 mls of water. In a separateflask, 7.01 g of glycine, 3.12 g of sodium hydroxide and 50 ml ofmethanol are mixed and allowed to stir for 30 minutes to form a solutionof the sodium salt of glycine. This solution is then added to the pyronesuspension with stirring. The resulting reaction mixture is allowed tostir at room temperature for five hours. 80 ml of water and 10 ml ofconcentrated hydrochloric acid is added. A precipitate forms within afew minutes. This is collected by filtration to yield 7.0 gms of methyl1-carboxymethyl-6-methyl-2-(4'-chlorophenyl)-4-oxonicotinate. mp(methanol/water)=224° C.

Example 21

4.0 g of 1-carboxymethyl-6-methyl-2-(4'-chlorophenyl)-4-oxonicotinate issuspended in 40 g of 5% aqueous sodium hydroxide solution and heated at80°-85° C. for two hours. The reaction mixture is cooled and acidifiedto give a white precipitate. This precipitate is collected by filtrationto yield 2.9 g of1-carboxymethyl-6-methyl-2-(4'-chlorophenyl)-4-oxonicotinic acid. mp(CH₃ CN)=158°-162° C.

Example 22

Part a

10 g of 3-methoxycarbonyl-6-methyl-2-(4'-chlorophenyl)-4-pyrone, 1.65 gglacial acetic acid and 100 ml of methanol are mixed in 500 ml flaskfitted with a magnetic stirring bar and sidearm addition funnel. 6.15 gof allylamine are slowly added (one hour addition time). Three hourslater 20 ml of water and 8 ml of concentrate HCl are added. Thisreaction mixture is allowed to stand at room temperature for one hour,then is poured into 400 ml of water and extracted with methylenechloride (2×100 ml). Removal of the solvent yields 10 g of crude methyl1-allyl-6-methyl-2-(4'-chlorophenyl)-4-oxonicotinate.

Part b

The crude oxonicotinate ester isolated above is suspended in 80 ml of 5%aqueous sodium hydroxide solution and heated at 85° C. for 2-21/2 hours.Acidification of this reaction mixture with dilute HCl provides 6.7 g of1-allyl-6-methyl-2-(4'-chlorophenyl)-4-oxonicotinic acid. mp(acetonitrile)=219°-221° C.

Example 47

6.0 g of 1,6-dimethyl-2-phenyl-4-oxonicotinic acid is suspended in 200ml of methanol. 1.0 g of sodium hydroxide is added. As soon as the aciddissolves a solution of 5.52 g of Br₂ in 50 ml of methanol is slowlyadded with stirring. The pH of the reaction mixture is maintained at 8-9by the addition of extra sodium hydroxide as required. A precipitate of3,5-dibromo-1,6-dimethyl-2-phenyl-pyrid-4-one forms. This material iscollected by filtration and discarded. Acidification of the clearfiltrate yields 3.4 g of 5-bromo-1,6-dimethyl-2-phenyl-4-oxonicotinicacid as a white solid. mp=252°-253° C. (acetonitrile).

B. N-alkyl-6-aryl-4-oxonicotinates

In another preferred aspect, this invention relates to compounds of theformula: ##STR28## wherein R₁ and R₂ are, independently, an optionallysubstituted (C₁ -C₆) alkyl or a (C₃ -C₆) alkenyl group; R₅ is hydrogenor halogen; Y is a hydrogen atom or a (C₁ -C₆) alkyl group; X is ahydrogen atom, a halogen atom, a trihalomethyl group, a (C₁ -C₆) alkylgroup, a nitro group, a cyano group or a (C₁ -C₆) alkoxy group; n is aninteger from 1 to 3; and the agronomically acceptable salts thereof.

Among the preferred compounds of the present invention are compounds ofGroup B, Formula XVIII, wherein R₁ and R₂ are, independently (C₁ -C₆)alkyl, (C₁ -C₄) haloalkyl, alkoxy (C₁ -C₄) alkyl (C₁ -C₄), aryl (C₁ -C₄)alkyl (C₁ -C₄) or (C₃ -C₆) alkenyl; Y is a hydrogen, (C₁ -C₆) alkyl, oran alkali or alkaline earth metal cation; R₅ is hydrogen or halogen; Xis hydrogen, halogen, trihalomethyl, (C₁ -C₆) alkyl, (C₁ -C₆) alkoxy,nitro or cyano; and n is an integer from 1 to 3.

Among the more preferred compounds of the present invention arecompounds of Group B, Formula XVIII, wherein R₁ and R₂ are,independently, (C₁ -C₄) alkyl; Y is hydrogen, CH₃, C₂ H₅, Na or K; R₅ ishydrogen or bromine; X is hydrogen, methoxy, methyl, trifluoromethyl,iodine, bromine, chlorine or fluorine and n is an integer from 1 to 3.

Among the most preferred compounds of this invention are compounds ofGroup B, Formula XVIII, where R₁ is a methyl or ethyl group; R₂ is amethyl, ethyl, or n-propyl group; R₅ is hydrogen or a bromine atom; X ishydrogen, methyl, trifluoromethyl; or bromine, chlorine or fluorine atomand n 1 or 2; and Y is a sodium or potassium cation, hydrogen, or amethyl or ethyl group; and the agronomically acceptable acid additionsalts thereof.

Typical compounds encompassed by the present invention include:

1,2-dimethyl-6-(3-fluorophenyl)-4-oxonicotinic acid;

2-n-butyl-1-ethyl-6-(4-methoxyphenyl)-4-oxonicotinic acid;

1-allyl-6-phenyl-2-n-propyl-4-oxonicotinic acid;

1-(3-chloropropyl)-2-methyl-6-phenyl-4-oxonicotinic acid;

1-(2-ethoxy methyl)-2-methyl-6-phenyl-4-oxonicotinic acid;

1-benzyl-2-n-propyl-6-(4-trifluoromethylphenyl)-4-oxonicotinic acid;

1,2-di-n-propyl-6-(4-fluorophenyl)-4-oxonicotinic acid;

1,2-dimethyl-6-phenyl-4-thioxonicotinic acid;

6-(4-chlorophenyl)-1,2-diethyl-4-oxonicotinic acid;

5-bromo-6-(4-chlorophenyl)-1,2-dimethyl-4-oxonicotinic acid;

6-(4-chlorophenyl)-1,2,5-trimethyl-4-oxonicotinic acid;

1,5-dimethyl-6-(4-fluorophenyl)-2-n-propyl-4-oxonicotinic acid;

1,2-dimethyl-6-(1-naphthyl)-4-oxonicotinic acid;

6-(3,5-dichlorophenyl)-1-methyl-2-n-propyl-4-oxonicotinic acid;

5-(4-chlorophenyl)-1-i-propyl-2-methyl-4-oxonicotinic acid;

2-i-propyl-1-methyl-6-phenyl-4-oxonicotinic acid

and metal salts thereof;

ethyl 1,2-dimethyl-6-(4-fluorophenyl)-4-oxonicotinate methyl6-(4-chlorophenyl)-1-ethyl-2-methyl-4-oxonicotinate

n-propyl 1-methyl-6-phenyl-2-n-propyl-4-oxonicotinate

i-propyl 1-allyl-6-(4-bromophenyl)-2-methyl-4-oxonicotinate

n-butyl 6-(3-chlorophenyl)-1-ethyl-2-n-propyl-4-oxonicotinate

n-hexyl 1,2-dimethyl-6-(4-iodophenyl)-4-oxonicotinate

and the agronomically acceptable salts thereof.

The Group B compounds of the present invention are prepared by varioussynthetic routes found in the art. In particular, the Group B compoundsof the present invention can be prepared by the following reactionsequence: ##STR29##

Alternatively, the Group B compounds can be prepared by the followingreaction sequence: ##STR30##

In the latter reaction sequence, the cyclization step yielded one ormore of the pyridones, XXVIII, XXIX and XXX. In general, a pyrolysis(neat) of the acyclic C-acylated intermediate (XXVII) yielded theoxonicotinic acid (XXX) directly. Cyclization of the acyclicintermediate (XXVII) in aprotic solvents at lower temperatures gavevaried results depending on reaction conditions and the X, R₁ and R₂substituent effects. In some cases, mixtures of products were obtained(ester, ester hydrochloride and acid), in other cases only one of theproducts was isolated.

The salts of the Group B oxonicotinic acids of the present invention canbe prepared by generally known procedures such as dissolving the acidsin a proctic solvent such as methanol, ethanol, water and the like andtreating them with an equivalent amount of a strong base such as sodiumor potassium hydroxide and the like, and recovering the salt either bystripping off the solvent or precipitating the solid out with adiethylether, hexane, benzene and the like.

Table IV below is presented to illustrate the more preferred compoundsof the present invention. This table and Table II in which theanalytical data is presented for these compounds are not to beinterpreted in any way as being limits on the breadth and scope of thepresent invention:

                                      TABLE IV                                    __________________________________________________________________________    LIST OF COMPOUNDS                                                              ##STR31##                                               (XXVIII)                                                       % Yield                             Example #                                                                            X                   R.sub.1                                                                            R.sub.2                                                                            Y    (from acid chloride)                                                                     Recryst.                 __________________________________________________________________________                                                         Solvent                  48     H                   Me   Me   Et   37.sup.a   MDC/ether                49     H                   Me   Me   EtHCl                                                                              37.sup.a   None                            H                   Me   Me   H    35.sup.a   MDC/ether                50     H                   Me   Me   Na   --         --                              H                   Et   Me   H    15.sup.b   CH.sub.3 CN              51     H                   Et   Me   Na   --         --                              H                   Pr   Me   H    23.sup.a   CH.sub.3 CN              52     H                   Pr   Me   Na   --         --                              H                    -n-Hexyl                                                                          Me   H    10.sup.a   methyl cyclohexane       53     H                    -n-Hexyl                                                                          Me   Na   --         --                              H                   Me   n-Pr H    30.sup.a   MDC/ether                54     H                   Me   n-Pr Na   --         --                              4-CH.sub.3          Me   Me   H    20.sup.b   CH.sub.3 CN              55     4-CH.sub.3          Me   Me   Na   --         --                              4-F                 Me   Me   H    16.sup.b   CH.sub.3 CN              56     4-F                 Me   Me   Na   --         --                       57     4-Cl                Me   Me   C.sub.2 H.sub.5                                                                    37.sup.a   Toluene                         4-Cl                Me   Me   H    25.sup.a   --                       58     4-Cl                Me   Me   Na   --         --                              4-Cl                Et   Me   H    17.sup.a   --                       59     4-Cl                Et   Me   Na   --         --                              4-Cl                 -n-Hexyl                                                                          Me   H     7.sup.a   Methyl cyclohexane       60     4-Cl                 -n-Hexyl                                                                          Me   Na   --         --                              3-CH.sub.3          Me   Me   H    23.sup.a   --                       61(HCl salt)                                                                         3-CH.sub.3          Me   Me   Na   --         --                              3,4-diCl            CH.sub.3                                                                           CH.sub.3                                                                           H    35.sup.a   --                       62     3,4-diCl            CH.sub.3                                                                           CH.sub.3                                                                           Na   --         --                              4-I                 CH.sub.3                                                                           CH.sub.3                                                                           H    34.sup.a   --                       63     4-I                 CH.sub.3                                                                           CH.sub.3                                                                           Na   --         --                              3-Cl                CH.sub.3                                                                           CH.sub.3                                                                           H    21.sup.a   --                       64     3-Cl                CH.sub.3                                                                           CH.sub.3                                                                           Na   --         --                              4-OCH.sub.3         CH.sub.3                                                                           CH.sub.3                                                                           H    4.2.sup.a                           65     4-OCH.sub.3         CH.sub.3                                                                           CH.sub.3                                                                           Na   --         --                       66(HCl salt)                                                                         4-Br                H    CH.sub.3                                                                           Et   24.sup.a   Methyl cyclohexane              4-Br                CH.sub.3                                                                           CH.sub.3                                                                           H    44.sup.a   --                       67     4-Br                CH.sub.3                                                                           CH.sub.3                                                                           Na   --         --                       68     4-Cl                CH.sub.2φ                                                                      CH.sub.3                                                                           Et   9.3.sup.a  --                              4-Cl                CH.sub.2φ                                                                      CH.sub.3                                                                           H     6.sup.a   --                       69     4-Cl                CH.sub.2φ                                                                      CH.sub.3                                                                           Na   --         --                       70(HCl salt)                                                                         4-CF.sub.3          CH.sub.3                                                                           CH.sub.3                                                                           Et   35.sup.a   --                              4-CF.sub.3          CH.sub.3                                                                           CH.sub.3                                                                           H    29.sup.a   --                       71     4-CF.sub.3          CH.sub.3                                                                           CH.sub.3                                                                           Na   --         --                       72(HCl salt)                                                                          ##STR32##          CH.sub.3                                                                           CH.sub.3                                                                           Et   38.5.sup.a --                              "                   CH.sub.3                                                                           CH.sub.3                                                                           H    35.sup.a   --                       73     "                   CH.sub.3                                                                           CH.sub.3                                                                           Na   --         --                       74(HCl salt)                                                                         4-Cl                CH.sub.3                                                                           CH.sub.3                                                                           Et   44.sup.a   --                       75(HCl salt)                                                                         4-CL                CH.sub.3                                                                            -n-C.sub.3 H.sub.7                                                                Et   23.sup.a   --                              4-Cl                CH.sub.3                                                                            -n-C.sub.3 H.sub.7                                                                H    17.sup.a   --                       76     4-Cl                CH.sub.3                                                                            -n-C.sub.3 H.sub.7                                                                Na   --         --                              H                   C.sub.2 H.sub.5                                                                     -n-C.sub.3 H.sub.7                                                                H    7.5.sup.a  --                       77(5-Br)                                                                             H                   C.sub.2 H.sub.5                                                                     -n-C.sub.3 H.sub.7                                                                Na   --         --                              H                   CH.sub.3                                                                           CH.sub.3                                                                           H    --         --                       78(5-Br)                                                                             H                   CH.sub.3                                                                           CH.sub.3                                                                           Na   --         --                       __________________________________________________________________________     .sup.a Xylene method                                                          .sup.b Direct pyrolysis                                                  

                  TABLE V                                                         ______________________________________                                        ANALYTICAL DATA                                                                ##STR33##                 (XXVIII)                                           Recryst.               Elemental Analysis.sup.a                               Example #                                                                             Solvent  mp (°C.)                                                                         % C  % H  % N  % X                                 ______________________________________                                        48               154       70.83                                                                              6.32 5.16 --                                                             71.03                                                                              6.39 5.33 --                                  49               211-3     --   --   --   --                                                   220-2.5   69.12                                                                              5.39 5.76 --                                                             68.65                                                                              5.34 6.10 --                                  50               --        --   --   --   --                                                   216-7     70.02                                                                              5.88 5.45 --                                                             70.26                                                                              5.93 5.69 --                                  51               --        --   --   --   --                                                   210-11    70.83                                                                              6.32 5.16 --                                                             70.40                                                                              6.29 5.60 --                                  52               --        --   --   --   --                                                   129-30    72.82                                                                              7.40 4.47 --                                                             72.33                                                                              7.35 4.73 --                                  53               --        --   --   --   --                                                   150       70.83                                                                              6.32 5.16 --                                                             70.41                                                                              6.23 5.19 --                                  54               --        --   --   --   --                                                   213-5     70.02                                                                              5.88 5.44 --                                                             69.38                                                                              5.69 5.20 --                                  55               --        --   --   --   --                                                   141-2     64.36                                                                              4.63 5.36 7.27                                                           63.16                                                                              4.35 6.14 6.94                                56               --        --   --   --   --                                  57               198 dec   62.85                                                                              5.28 4.58 --                                                             62.82                                                                              5.31 4.66 --                                                   236-238 dec                                                                             60.55                                                                              4.36 5.04 --                                                             60.33                                                                              4.34 5.18 --                                                   212-214 dec                                                                             61.75                                                                              4.84 4.80 --                                                             61.11                                                                              4.61 5.17 --                                  58               --        --   --   --   --                                  59               --        --   --   --   --                                                   127-129   65.60                                                                              6.38 4.03 --                                                             65.78                                                                              6.54 4.21 --                                  60               --        --   --   --   --                                                   218-220 dec                                                                             70.02                                                                              5.88 5.44 --                                                             69.75                                                                              5.96 5.62 --                                  61               --        --   --   --   --                                                   271-2 dec 45.86                                                                              3.85 3.82 --                                                             44.82                                                                              3.22 4.06 --                                  62               297-9 dec --   --   --   --                                                             --   --   --   --                                                   283-4 dec 45.55                                                                              3.28 3.79 --                                                             45.63                                                                              3.37 3.79 --                                  63               >300      --   --   --   --                                                             --   --   --   --                                                   265-6 dec --   --   --   --                                                             --   --   --   --                                  64               --        --   --   --   --                                                             --   --   --   --                                                   226-236 dec                                                                             65.92                                                                              5.53 5.13 --                                                             65.29                                                                              5.34 5.68 --                                  65               --        --   --   --   --                                                             --   --   --   --                                  66               114       48.34                                                                              4.06 3.76 --                                                             48.45                                                                              4.04 3.68 --                                                   269-271 dec                                                                             52.19                                                                              3.76 4.35 --                                                             52.04                                                                              3.69 4.28 --                                  67               294-6 dec --   --   --   --                                                             --   --   --   --                                  68      Toluene  201-2.5   69.20                                                                              5.28 3.67 --                                                             68.93                                                                              5.29 3.54 --                                          --       169-173   67.89                                                                              4.56 3.96 --                                                             67.83                                                                              4.50 4.25 --                                  69      --       --        --   --   --   --                                                             --   --   --   --                                  70      --       212-214 dec                                                                             54.33                                                                              4.53 3.73 --                                                             53.92                                                                              4.65 4.01 --                                          --       220-222 dec                                                                             57.88                                                                              3.89 4.50 --                                                             58.07                                                                              3.88 5.38 --                                  71      --       >310      --   --   --   --                                                             --   --   --   --                                  72      --       212-214 dec                                                                             67.13                                                                              5.63 3.91 --                                                             67.20                                                                              5.59 3.40 --                                          --       260-3 dec 73.70                                                                              5.15 4.78 --                                                             73.34                                                                              5.14 4.76 --                                  73      --       225-235 dec                                                                             --   --   --   --                                                             --   --   --   --                                                                            X = Cl                              74      --       213-215 dec                                                                             56.15                                                                              5.07 4.09 20.72                                                          55.79                                                                              4.95 4.62 20.34                               75      --       200-2 dec Poor elemental analysis                                    --       184-187   62.85                                                                              5.28 4.58 --                                                             62.00                                                                              5.27 4.89 --                                  76      --       168-210 dec                                                                             --   --   --   --                                                             --   --   --   --                                          --       121-3 dec 71.56                                                                              6.71 4.91 --                                                             71.67                                                                              6.76 5.29 --                                  77      --       80-100    --   --   --   --                                                             --   --   --   --                                          H.sub.3 CCN                                                                            257-8     52.19                                                                              3.75 4.35 Br 24.81                                                       52.55                                                                              3.76 4.36 Br 25.18                            78      --       --        --   --   --   --                                                             --   --   --   --                                  ______________________________________                                         .sup.1 Generally the elemental analysis for aNa salts were either not         performed or gave poor results due to the hygroscopic nature of the           results.                                                                 

The following examples are presented to illustrate the methods forpreparation of the compounds of the present invention. Again theseexamples are not to be interpreted as being limits upon the breadth andscope of the present invention.

β-Chlorocinnamoyl chloride

A solution of 60 g (0.312 mol) ethyl benzoyl acetate in 96 ml (150 g) ofphosphorous trichloride is added dropwise to 150 g (0.72 mol) ofphosphorous pentachloride under nitrogen. The suspension that forms iscautiously brought to reflux temperature (HCl evolution observed) and isrefluxed and stirred for 2-21/2 hrs. The solution that forms is strippedof phosphorous trichloride and phosphorous oxychloride at atmosphericpressure (76°-82° C.). The pot residue is distilled at 97°-108° C./0.75mm to give 54 g (86% yield) of product as an isomeric mixture.

β-Chloro(4-chloro)cinnamoylchloride

A solution of 22.67 g (0.1 mol) ethyl (4-chloro benzoyl) acetate in 70ml of phosphorous trichloride is added dropwise to 52.0 g (0.25 mol) ofphosphorous pentachloride under nitrogen (HCl evolution observed). Thesuspension that forms is stored at room temperature for 1/2 hr. and atreflux temperature for 21/2 hrs. The solution that forms is stripped ofphosphorous trichloride, phosphorous oxychloride and phosphorouspentachloride at 80°-90° C. (pot temperature)/ambient pressure, 90°-110°C. (pot temperature)/40 mm and 90°-130° (pot temperature)/0.15 mm. Ayield of 23.35 g (99%) of crude product is obtained as the pot residue;

Ethyl β-methylamino crotonate

186 g (1.43 mol) of ethyl acetoacetate is added dropwise over a periodof 10 min. to a solution of 450 ml. of methylamine (40% in water) in 150ml. of water (exotherm from room temperature to 56° C. observed). Themixture is stirred at room temperature for 2 hrs. and is extracted withchloroform. The chloroform extract is washed with water, dried overmagnesium sulfate and concentrated in vacuo. The residue oil is vacuumdistilled at 76°-83° C./0.1 mm to afford 143.6 g (70% yield) of yellowoil.

Ethyl 3-methylamino-2-hexeneoate

A solution of 31.64 g (0.2 mol) ethyl butyryl acetate and 5 ml ofethanol is added dropwise over a period of 5 min. to a solution of 38.7g (0.6 mol) ethylamine (70% in water) and 50 ml of water (exotherm from28° C. to 33° C. observed). The mixture is stirred at room temperaturefor 18 hrs. and is extracted with three 100 ml portions of methylenedichloride (MDC). The methylene dichloride extract is dried overmagnesium sulfate and concentrated in vacuo to afford 30.7 g (83% yield)of product, a colorless oil.

Example 48 Ethyl 1,2-dimethyl-6-phenyl-4-oxonicotinate

2.0 g (0.0065 mol.) of ethyl 1,2-dimethyl-6-phenyl-4-oxonicotinatehydrochloride (see Example 49 below) is dissolved in water and treatedwith dilute sodium hydroxide (pH adjusted to about 8). The precipitateformed is isolated by vacuum filtration to afford 1.9 g of product, mp154° C. (MDC/ether recrystallization).

Example 49 Ethyl 1,2-dimethyl-6-phenyl-4-oxonicotinate Hydrochloride

9.2 g (0.046 mol.) of β-chlorocinnamoyl chloride (isomermixture)dissolved in 75 ml of methylene dichloride is added dropwise to asolution of 6.6 g (0.046 mol) of ethyl β-methylaminocrotonate and 7.4 g(0.0937 mol) of pyridine in 100 ml of methylene dichloride undernitrogen (5 min. addition time, slight exotherm from 25° to 35° C. Thereaction mixture is allowed to stand for 11/2 hrs. The methylenedichloride layer is isolate and passed through a 2 inch column of silicagel. The column is eluted with an additional 200 ml of methylenedichloride and the light yellow colored eluate is concentrated in vacuoto yield 15 g of ethyl 2-(3-phenyl-3-chloro) acrylyl-3-methylaminocrotonate, an oil.

15 g (0.0488 mol) of ethyl 2-(3-phenyl-3-chloro) acrylyl-3-methylaminocrotonate is suspended in 150 ml of xylene and refluxed for 3 hrs.The reaction mixture is cooled and the suspension is vacuum filtered.The filter cake is dried to afford 5.7 g (38% yield) of product, mp211°-213° C.

Example 50 Sodium 1,2-dimethyl-6-phenyl-4-oxonicotinate

42 g (0.1366 mol) of ethyl 2-(3-phenyl-3-chloro) acrylyl-3-methylaminocrotonate is placed in a flask and heated to 140° C. under nitrogen(nitrogen sparge started at this time). The pot temperature was slowlyraised to 157° C. over a period of 40 min. The reaction mixture wascooled and extracted into 5% aqueous sodium hydroxide. Acidification ofthe basic extracts provided 10.0 g (30% yield) of1,2-dimethyl-6-phenyl-4-oxonicotinic acid, mp 220°-225° C. (MDC/ether).

15 g (0.01617 mol) of 1,2-dimethyl-6-phenyl-4-oxonicotinic acid issuspended in 200 ml of methanol and to it there is added 2.71 g (0.0678mol) of sodium hydroxide pellets. The solution formed is concentrated invacuo to afford 15 g (92% yield) of product.

Example 54 Sodium 1-methyl-6-phenyl-2-propyl-4-oxonicotinate

A solution of 11.4 g (0.057 mol) β-chlorocinnamoyl chloride and 75 ml ofmethylene dichloride is added over a period of 20 min. to a solution of8.6 g (0.054 mol) ethyl 3-methylamino-2-hexenoate, 9.0 g (0.114 mol)pyridine and 100 ml of methylene dichloride under nitrogen (slightexotherm from 25°-36° C.). The mixture is allowed to stand at roomtemperature for 11/2 hrs. and is washed with water. The methylenedichloride solution is passed through a 2 inch column of silica gel andis concentrated in vacuo to afford 13 g of ethyl(3-phenyl-3-chloro)acrylyl-3-methylamino-2-hexeneoate, an oil.

13 g (0.0387 mol) of ethyl (3-phenyl-3-chloro)acrylyl-3-methyl-amino-2-hexeneoate is dissolved in 200 ml of xylene andis refluxed and stirred for 4 hrs. The solution is washed with 30 ml of6N hydrochloric acid. The aqueous washings are neutralized and theprecipitate formed is isolated to afford 4.5 g of ethyl1-methyl-6-phenyl-2-propyl-4-oxonicotinate.

4.5 g (0.015 mol) of ethyl 1-methyl-6-phenyl-2-propyl-4-oxonicotinate issuspended in 60 g of 5% sodium hydroxide in a 1:1 mixture of methanoland water. The mixture is heated at 85° C. and stirred for 21/2 hrs. Thesolution formed is acidified and the suspension formed is vacuumfiltered. The filter cake is dried to afford 2.7 g of1-methyl-6-phenyl-2-propyl-4-oxonicotinic acid, mp 150° C. (MDC/ether).An additional 0.5 g of 1-methyl-6-phenyl-2-propyl-4-oxonicotinic acid isobtained by extraction of the xylene solution with 30 ml of 1% sodiumhydroxide and acidification of the basic extract.

2.1 g (0.0067 mol) of 1-methyl-6-phenyl-2-propyl-4-oxonicotinic acid issuspended in 50 ml of methanol and to it there is added 0.295 g (0.0074mol) of sodium hydroxide pellets. The solution is concentrated in vacuoto afford 1.9 g (97% yield) of product.

Example 57 Ethyl 6-(4-chlorophenyl)-1,2-dimethyl-4-oxonicotinate

A solution of 10 g (0.0425 ml) β-chloro(4-chloro) cinnamoyl chloride in50 ml of methylene dichloride is added dropwise over a 10 min. period toa solution of 6.08 g (0.0425 mol) ethyl β-methylaminocrotonate, 6.72 g(0.085 mol) of pyridine and 200 ml of methylene dichloride (slightexotherm from 25° to 34° C.). The mixture is stirred at room temperaturefor 18 hrs. and is washed with water. The methylene dichloride solutionis vacuum filtered through 25 g of silica gel and the filtrate isconcentrated in vacuo to afford 12.55 g of ethyl[3-(4-chlorophenyl)-3-chloro] acrylyl-3-methylamino-crotonate, an oil.

A solution of 12.55 g (0.037 mol) ethyl [3-(4-chlorophenyl)-3-chloro]acrylyl-3-methylamino crotonate in 50 ml of xylene is refluxed andstirred for 21/2 hrs. under nitrogen. The suspension formed is vacuumfiltered to afford 6.5 g (52% yield) of ethyl6-(4-chlorophenyl)-1,2-dimethyl-4-oxonicotinate hydrochloride (Example27).

A suspension of 6.5 g (0.019 mol) ethyl6-(4-chlorophenyl)-1,2-dimethyl-4-oxonicotinate hydrochloride in 150 mlof water is treated with sodium hydroxide (pH adjusted to about 8). Thesuspension formed is vacuum filtered and the filter cake is washed withwater and dried to afford 4.9 g (43.3% yield) of product, a white solid,mp 198° C. dec (Toluene).

Example 58 Sodium 6-(4-Chlorophenyl)-1,2-dimethyl-4-oxonicotinate

1.5 g (0.019 mol) of 50% aqueous sodium hydroxide is added to asuspension of 2.9 g (0.0095 mol) ethyl6-(4-chlorophenyl)-1,2-dimethyl-4-oxonicotinate in 75 ml of water. Themixture is refluxed and stirred for 15 min. and cooled to roomtemperature. The solution is extracted with methylene dichloride and theaqueous solution is acidified to pH 1 with 12N hydrochloric acid. Thesuspension formed is vacuum filtered and the filter cake is dried toafford 1.8 g (68% yield) of6-(4-chlorophenyl)-1,2-dimethyl-4-oxonicotinic acid, mp 236°-238° C.dec.

0.52 g (0.0065 mol) of 50% aqueous sodium hydroxide is added to asuspension of 1.8 g (0.0065 mol)6-(4-chlorophenyl)-1,2-dimethyl-4-oxonicotinic acid in 35 ml ofmethanol. The solution formed is allowed to stand at room temperaturefor 1 hr. and then is concentrated in vacuo. The concentrate is washedwith two (25 ml) portions of diethyl ether and dried to afford 1.7 g(87% yield) of product.

Example 67 Sodium 6-(4-Bromophenyl)-1,2-dimethyl-4-oxonicotinate

A solution of 12 g (0.043 mol) β-chloro(4-bromo) cinnamoyl chloride in25 ml of methylene dichloride is added dropwise over a 3 min. period toa solution of 6.15 g (0.043 mol.) ethyl β-methylamino crotonate, 6.8 g(0.086 mol) of pyridine and 200 ml of methylene dichloride (slightexotherm from 25° C. to 33° C.). The solution is stirred at roomtemperature for 3 days and is washed with 200 ml of water. The methylenedichloride solution is vacuum filtered through 25 g of silica gel andthe filtrate is concentrated in vacuo to afford 11 g (66% yield) ofethyl [3-(4-bromophenyl)-3-chloro] acrylyl-3-methylamino crotonate, abrown oil.

11 g (0.0284 mol) of ethyl [3-(4-bromophenyl)-3-chloro]acrylyl-3-methylamino crotonate is dissolved in 10 ml of toluene and 50ml of xylene and is refluxed and stirred for 4 hrs. under nitrogen. Thesuspension formed is stirred at room temperature for 18 hrs. and isvacuum filtered. The filter cake is washed with hexane and dried toafford 5.3 g (48.0%) of ethyl6-(4-bromophenyl)-1,2-dimethyl-4-oxonicotinate hydrochloride, mp206°-210° C. dec.

5.3 g (0.014 mol) of ethyl6-(4-bromophenyl)-1,2-dimethyl-4-oxonicotinate hydrochloride issuspended in 100 ml of water and to it there is added 5 g (0.0625 mol)of 50% aqueous sodium hydroxide. The mixture is refluxed and stirred for1 hr. and the solution formed is cooled to room temperature. Thesolution is extracted with methylenedichloride and the aqueous solutionis acidified to pH 1 with 12N hydrochloric acid. The suspension formedis vacuum filtered and the filter cake is washed with water and dried toafford 4 g (89% yield) of 6-(4-bromophenyl)-1,2-dimethyl-4-oxonicotinicacid, mp 269°-271° C. dec.

2 g (0.0062 mol) of 6-(4-bromophenyl)-1,2-dimethyl-4-oxonicotinic acidis suspended in 50 ml of methanol and to it there is added 0.5 g (0.0062mol) of 50% aqueous sodium hydroxide. The solution formed is allowed tostand at room temperature for 1 hr. and is concentrated in vacuo. Theconcentrate is washed with 50 ml of diethyl ether and dried to afford1.9 g (89% yield) of product.

Example 75 Ethyl 6-(4-chlorophenyl)-1-methyl-2-n-propyl-4-oxonicotinatehydrochloride

A solution of 15 g (0.064 mol) β-chloro (4-chloro) cinnamoyl chloride in50 ml of methlene dichloride is added dropwise over a 3 min. period to astirred solution of 10.9 g (0.064 mol) ethyl 3-methylamino-2-hexeneoateand 10.1 g (0.128 mol) of pyridine in 200 ml of methylene dichloride(slight exotherm from 25° C. to 34° C.). The solution formed is stirredat room temperature for 18 hrs. and is washed with water. The methylenedichloride solution is vacuum filtered through silica gel and thefiltrate is concentrated in vacuo to afford 18.5 g (78% yield) of ethyl[3-(4-chlorophenyl)-3-chloro] acrylyl-3-methylamino-2-hexeneoate, abrown oil.

A solution of 18.5 g (0.05 mol) of ethyl [3-(4-chlorophenyl)-3-chloro]acrylyl-3-methylamino-2-hexeneoate in 15 ml of toluene and 60 ml ofxylene is refluxed and stirred for 3 hrs. under nitrogen. The suspensionformed is allowed to stand at room temperature for 8 days and is vacuumfiltered. The filter cake is washed with toluene and hexane and dried toafford 4.3 g (23% yield) of product, mp 200°-202° C. dec.

Example 76 Sodium 6-(4-chlorophenyl)-1-methyl-2-n-propyl-4-oxonicotinate

4.0 g (0.05 mol) of 50% aqueous sodium hydroxide is added to asuspension of 2.7 g (0.01 mol) ethyl6-(4-chlorophenyl)-1-methyl-2-n-propyl-4-oxonicotinate hydrochloride in50 ml of water and 10 ml of ethanol. The mixture is refluxed and stirredfor 3 hrs, allowed to stand at room temperature for 18 hrs., refluxedfor an additional 1 hr. and cooled to room temperature. The solutionformed is extracted with three 50 ml portions of methylene dichlorideand the aqueous solution is acidified to pH 1 with 12N hydrochloricacid. The suspension formed is stirred at room temperature for 3 hrs.and is vacuum filtered. The filter cake is dried to afford 1.65 g (54%yield) of 6-(4-chlorophenyl)-1-methyl-2-n-propyl-4-oxonicotinic acid, mp184°-187° C.

0.42 g (0.0052 mol) of 50% aqueous sodium hydroxide is added to asuspension of 1.6 g (0.0052 mol)6-(4-chlorophenyl)-1-methyl-2-n-propyl-4-oxonicotinic acid in 25 ml ofmethanol. The solution formed is allowed to stand at room temperaturefor 1 hr. and is concentrated in vacuo. The concentrate is dried toafford 1.5 g (88% yield) of product.

Example 78 Sodium 5-Bromo-1,2-dimethyl-6-phenyl-4-oxonicotinate

2.0 g (0.0125 mol) of bromine dissolved in 50 ml. of methanol is addeddropwise over a 15 min. period to a solution of 2.7 g (0.00877 mol)ethyl 1,2-dimethyl-6-phenyl-4-oxonicotinate hydrochloride (Example 2) in15 ml of methanol and 15 ml of water. The suspension formed is vacuumfiltered and the filter cake, a yellow solid, is suspended in 60 g of 5%aqueous sodium hydroxide. The mixture is stirred and heated at 85° C.for 21/2 hrs. and is acidified with hydrochloric acid. The suspensionformed is vacuum filtered to afford 2.4 g (85% yield) of5-bromo-1,2-dimethyl-6-phenyl-4-oxonicotinic acid, mp 257°-258° C. (CH₃CN).

2.1 g (0.065 mol) of 5-bromo-1,2-dimethyl-6-phenyl-4-oxonicotinic acidis suspended in 50 ml of methanol and to it there is added 0.29 g (0.007mol) of sodium hydroxide pellets. The solution formed is concentrated invacuo to afford 2.1 g (94% yield) of product.

C. N-alkyl-5-aryl-4-oxonicotinates

In yet another preferred aspect, this invention relates to compounds ofthe formula: ##STR34## wherein R₁ is an optionally substituted (C₁ -C₆)alkyl group; R₂ is a (C₁ -C₄) alkyl group; R₆ is a hydrogen atom or a(C₁ -C₄) alkyl group; Y is a hydrogen atom or a (C₁ -C₆) alkyl group orradical; X is a hydrogen atom, a halogen atom, a trihalomethyl group, a(C₁ -C₆) alkyl group, a nitro group, a cyano group or a (C₁ -C₄) alkoxygroup; and n is the integer 1 or 2 ; and the agronomically acceptablesalts thereof.

Among the preferred compounds of the present invention are compounds ofGroup C, Formula (XXXI) wherein R₁ and R₂ are, independently, (C₁ -C₆)alkyl, (C₁ -C₄) haloalkyl, alkoxy (C₁ -C₄), aryl (C₆ -C₁₀) alkyl (C₁-C₄), or (C₃ -C₆) alkenyl; Y is hydrogen, (C₁ -C₆) alkyl, or an alkalior alkaline earth metal cation; R₆ is hydrogen or (C₁ -C₄) alkyl; X ishydrogen, halogen, trihalomethyl, (C₁ -C₆) alkoxy, nitro or cyano; and nis an integer from 1 to 3.

Among the more preferred compounds of the present invention arecompounds of Group C, Formula (XXXI) wherein R₁ is (C₁ -C₆) alkyl, R₂ is(C₁ -C₃) alkyl; R₆ is hydrogen or (C₁ -C₄) alkyl, Y is hydrogen, methyl,ethyl or a sodium or potassium cation, X is hydrogen, (C₁ -C₆) alkyl orhalogen and n is the integer 1 or 2.

Among the most preferred compounds of this invention are compounds ofGroup C, Formula (XXXI) wherein R₁ is a methyl or ethyl group; R₂ is amethyl group; R₆ is a hydrogen radical or a methyl group; and Y is ethylor a sodium or potassium cation; and the agronomically acceptable acidsalts thereof.

Typical compounds encompassed by the present invention include:

1,2-dimethyl-5-phenyl-4-oxonicotinic acid

1-ethyl-2-methyl-5-phenyl-4-oxonicotinic acid

1,2,6-trimethyl-5-phenyl-4-oxonicotinic acid

1,2-diethyl-5-phenyl-4-oxonicotinic acid

2-ethyl-1-methyl-5-phenyl-4-oxonicotinic acid

1,2-dimethyl-5-(4-chlorophenyl)-4-oxonicotinic acid

1-ethyl-2-methyl-5-(4-chlorophenyl)-4-oxonicotinic acid

1-ethyl-2,6-dimethyl-5-(4-chlorophenyl)-4-oxonicotinic acid

1,2-diethyl-5-(4-chlorophenyl)-4-oxonicotinic acid

1,2-dimethyl-5-(3-chlorophenyl)-4-oxonicotinic acid

1-ethyl-2-methyl-5-(3-chlorophenyl)-4-oxonicotinic acid

1-ethyl-2,6-dimethyl-5-(3-chlorophenyl)-4-oxonicotinic acid

1-ethyl-2-methyl-5-(4-trifluoromethylphenyl)-4-oxonicotinic acid

1,2-dimethyl-5-(4-fluorophenyl)-4-oxonicotinic acid

1-ethyl-2-methyl-5-(4-fluorophenyl)-4-oxonicotinic acid

1-ethyl-2-methyl-5-(3-fluorophenyl)-4-oxonicotinic acid

1-ethyl-2-methyl-5-(4-bromophenyl)-4-oxonicotinic acid

1,2-dimethyl-5-(3,4-dichlorophenyl)-4-oxonicotinic acid

1-ethyl-2-methyl-5-(3,4-dichlorophenyl)-4-oxonicotinic acid

1,2,6-trimethyl-5-(3,4-dichlorophenyl)-4-oxonicotinic acid

1,2-diethyl-6-methyl-5-(3,4-dichlorophenyl)-4-oxonicotinic acid

2-ethyl-1,6-dimethyl-5-(3,4-dichlorophenyl)-4-oxonicotinic acid

1-ethyl-2-methyl-5-(2,4-dichlorophenyl)-4-oxonicotinic acid

1-ethyl-2-methyl-5-(4-methylphenyl)-4-oxonicotinic acid

and the agronomically acceptable salts thereof.

The compounds of the present invention can be prepared by varioussynthetic routes found in the art.

Tables VI and VII below are presented to illustrate the more preferredcompounds of this aspect of the present invention and related compoundsand the analytical data for these compounds. ##STR35##

                  TABLE VI                                                        ______________________________________                                        List of Group C Compounds                                                     Example   X.sub.1  R.sub.1   R.sub.2                                                                              R.sub.6                                                                             Y                                   ______________________________________                                        79        H        H         H      Me    Et                                  80        H        H         H      Me    H                                    80a      H        H         H      Me    Na                                  81        H        Et        H      Me    H                                    81a      H        Et        H      Me    Na                                  82        H        Me        Me     H     Et                                  83        H        Me        Me     H     H                                    83a      H        Me        Me     H     Na                                  84        H        Et        Me     H     H                                    84a      H        Et        Me     H     Na                                  85        H        Et        Me     Me    H                                    85a      H        Et        Me     Me    Na                                  86        H        H         Me     Me    H                                    86a      H        H         Me     Me    Na                                  87        4-Cl     Me        Me     H     Et                                  88        4-Cl     Me        Me     H     H                                    88a      4-Cl     Me        Me     H     Na                                  89        4-Cl     Me        Me     Me    H                                    89a      4-Cl     Me        Me     Me    Na                                  90        4-Br     Me        Me     H     H                                    90a      4-Br     Me        Me     H     Na                                  91        4-Br     Me        n-Pr   H     H                                    91a      4-Br     Me        NPr    H     Na                                  92        4-Br     n-Hex     Me     H     H                                    92a      4-Br     NHex      Me     H     Na                                  93        4-Br     Me        Me     Me    H                                    93a      4-Br     Me        Me     Me    H                                   94        4-Cl     φ     Me     H     H                                    94a      4-Cl     φ     Me     H     Na                                  95        H        4-Fφ  Me     H     Et                                  96        H        4-Fφ  Me     H     H                                    96a      H        4-Fφ  Me     H     Na                                  ______________________________________                                    

                  TABLE VII                                                       ______________________________________                                        Analytical Data - Group C Compounds                                           Example  mp         % C    % H    % N  % X                                    ______________________________________                                        79        178-80    --     --     --   --                                     80       265-7      --     --     --   --                                      80a     --         --     --     --   --                                     81       177-8      --     --     --   --                                      81a     --         --     --     --   --                                     82        148-50    70.83  6.32   5.16 --                                                         70.71  6.40   5.23 --                                     83       227-8      69.12  5.34   5.76 --                                                         68.80  5.51   6.07 --                                      83a     --         --     --     --   --                                     84        167-70    70.02  5.88   5.45 --                                                         70.04  6.04   5.57 --                                      84a     --         --     --     --   --                                     85       163-5      70.83  6.31   5.16 --                                                         70.78  6.49   5.82 --                                      85a     --         --     --     --   --                                     86       272-3      69.12  5.39   5.76 --                                                         69.00  5.41   5.95                                         86a     --         --     --     --   --                                     87       200-1      62.85  5.28   4.58 11.60                                                      63.14  5.33   4.79 11.58                                  88        239-40    60.55  4.36   5.04 12.77                                                      60.33  4.27   5.28 12.82                                   88a     --         --     --     --   --                                     89       240-3      61.75  4.84   4.80 12.16                                                      62.13  4.90   4.96 12.26                                   89a     --         --     --     --   --                                     90       266-8      52.19  3.75   4.35 24.81                                                      52.32  3.69   4.39 34.75                                   90a     --         --     --     --   --                                     91       237-9      54.87  4.61   4.00 22.82                                                      55.22  4.68   4.21 22.21                                   91a     --         --     --     --   --                                     92        148-50    58.17  5.65   3.57 20.37                                                      57.86  5.51   4.51 20.23                                   92a     --         --     --     --   --                                     93        228-30    53.59  4.20   4.17 23.77                                                      53.65  4.19   4.64 23.34                                   93a     --         --     --     --   --                                     94       208-9      67.16  4.15   4.12 10.44                                                      67.48  4.16   4.37 10.65                                   94a     --         --     --     --   --                                     95        179-81    71.78  5.16   3.99  5.41                                                      71.38  5.26   4.07  5.25                                  96       197-8      70.58  4.36   4.33  5.88                                                      70.32  4.25   4.56  5.80                                   96a     --         --     --     --   --                                     ______________________________________                                    

The following examples are presented to illustrate the methods forpreparation of the Group C compounds of the present invention.

EXPERIMENTAL PROCEDURES Example 79

The following procedure is a modified version of one reported byKametani, et al., J. Het. Chem., 1977, 14, 477.

25 g. of diethyl aminomethylenemalonate, 18 g. of phenylacetonedimethylketal, 300 ml. of dry diphenyl ether and 1.0 g. of TSA.H₂ O weremixed and heated under a nitrogen atmosphere at 135°-145° C. for threehours. The mixture was then brought to reflux. After 30 minutes thesolution was cooled and extracted with 200 ml. of 21/2% aqueous NaOHsolution. The basic extracts were acidified yielding a precipitate ofethyl 6-methyl-5-phenyl-4-oxonicotinate. Recrystallization of thismaterial from methylene chloride/ether provided 12.3 g. of white solid,m.p.=178°-180° C.

Example 80

4.0 g. of 6-methyl-5-phenyl-4-oxonicotinate was suspended in 40 g. of 5%aqueous NaOH solution. This suspension was heated at 85°-90° C. forthree hours, cooled, acidified. The resulting precipitate of6-methyl-5-phenyl-4-oxonicotinic acid was dried and recrystallized fromacetonitrile. Yield=2.3 g.; m.p.=265°-267° C.

Example 80A

2.31 g. of 6-methyl-5-phenyl-4-oconicotinic acid was mixed with 0.44 g.of NaOH and 50 ml. of methanol. Evaporation of the solvent provided 2.4g. of sodium 6-methyl-5-phenyl-4-oxonicotinate as a glassy solid.

Example 81

Part A

Ethyl 1-ethyl-6-methyl-5-phenyl-4-oxonicotinate was prepared accordingto the procedure described by Kametani, et al., J. Het. Chem., 1977, 14,477.

Part B

Crude ethyl 1-ethyl-6-methyl-5-phenyl-4-oxonicotinate was suspended in80 g. of 5% aqueous NaOH solution and heated on a steambath for onehour. Acidification of the aqueous mixture gave1-ethyl-6-methyl-5-phenyl-4-oxonicotinatic acid as a white precipitate(3.3 g.). Recrystallization from acetonitrile provided material meltingat 177°-178° C.

Example 81A

3.13 g. of 1-ethyl-6-methyl-5-phenyl-4-oxonicotinic acid, 0.54 g. ofNaOH and 50 ml. of methanol were mixed. Evaporation of the solventprovided 3.7 g. of glassy sodium1-ethyl-6-methyl-5-phenyl-4-oxonicotinic acid.

Example 82

Part A

16.5 g. of ethyl β-methylaminocrotonate, 9.3 ml. of pyridine and 300 ml.of methylene chloride were mixed in a flask fitted with a magneticstirring bar, a sidearm addition funnel and a CaCL₂ drying tube. 18.3 g.of phenylacetyl chloride was slowly added. Two hours later the reactionmixture was poured into water. The organic layer was separated andevaporated yielding 30 g. of crude ethyl3-oxo-4-phenyl-2-(methylamino-ethylidene)butrate as a yellow oil.

Part B

13.1 g. of crude ethyl 3-oxo-4-phenyl-2-(methylamino-ethylidene)butrate,5.95 g. of dimethylformamide dimethyl acetal and 25 ml. of drydimethylformamide were heated to 80° C. under a nitrogen atmosphere for19 hours. 2.0 ml. of triethylamine and an additional 5.95 g. ofdimethylformamide dimethyl acetal were added and the reaction was heatedat 80° C. for another 6 hours. The reaction was cooled, poured intowater and extracted with methylene chloride. The organic extracts werethoroughly washed with water and dilute CHl and evaporated. The residueof ethyl 1,2-dimethyl-5-phenyl-4-oxonicotinate was tritrated with etherand recrystallized from methylene chloride/ether. Yield=3.2 g.;m.p.=148°-150° C.,

Example 83

5.8 g. of ethyl 1,2-dimethyl-5-phenyl-4-oxonicotinate was suspended in60 ml. of 5% aqueous NaOH solution and heated on a steambath for 21/2hours. The mixture was cooled and acidified. The resulting solid wasrecrystallized from acetonitrile to yield1,2-dimethyl-5-phenyl-4-oxonicotinic acid as tan needles. m.p.=227°-228°C.

Example 83A

1.69 g. of 1,2-dimethyl-5-phenyl-4-oxonicitonic acid was mixed with 0.31g. of NaOH and 50 ml. of methanol. Evaporation of the solid provided 1.9g. of sodium 1,2-dimethyl-5-phenyl-4-oxonicotinic acid as a glassysolid.

Example 85

Part A

42.4 g. of ethyl β-ethylaminocrotonate, 23.7 g. of pyridine and 700 ml.of methylene chloride were mixed. 46.4 g. of phenylacetyl chloride wasadded slowly with stirring. Three hours later the mixture was pouredinto water and the organic layer was separated and evaporated yielding99 g. of ethyl 3-oxo-4-phenyl-2-(ethylaminoethylidene)butrate as ayellow oil.

Part B

13.8 g. of 3-oxo-4-phenyl-2-(ethylaminoethylidene)butrate, 13.3 g. ofdimethylacetamide dimethyl acetal, 25 g. of dry dimethylformamide and 2ml. of triethylamine were heated at 75°-80° C. under nitrogen for 24hours. The reaction mixture was cooled and poured into 600 ml. of water.The aqueous suspension was acidified with HCl and extracted withmethylene chloride. Evaporation of the solvent provide 10.5 g. of crudeethyl 1-ethyl-2,6-dimethyl-5-phenyl-4-oxonicotinate as a brown oil.

Part C

10.5 g. of crude ethyl 1-ethyl-2,6-dimethyl-5-phenyl-4-oxonicotinate wassuspended in 100 g. of 5% aqueous NaOH solution and heated on asteambath for 2 hours. The reaction mixture was cooled and acidified.Extraction with methylene chloride and subsequent evaporation of thesolvent yielded 3 g. of 1-ethyl-2,6-dimethyl-5-phenyl-4-oxonicotinate.Recrystallization from acetonitriel provided material with a meltingpoint of 163°-165° C.

Example 85A

1.5 g. of 1-ethyl-2,6-dimethyl-5-phenyl-4-oxonicotinate, 0.24 g. of NaOHand 40 ml. of methanol were mixed. Evaporation of the solvent provided1.4 g. of sodium 1-ethyl-2,6-dimethyl-5-phenyl-4-oxonicotinate as aglass, solid.

Example 86

Part A

2.68 g. of diethyl aminoethylidene malonate, 18 g. of phenylacetonedimethyl ketal, 1 g. of toluenesulfonic acid monohydrate and 300 ml. ofdiphenyl ether were heated at 180° C. for 2 hours. Methanol and ethanolbegan to distill out of the reaction flask and was collected in aDean-Stark trap. The reaction mixture was then allowed to heat up to205° C. for an addition 3 hours. A solid formed upon cooling. This wascollected by filtration, yielding 4.6 g. of ethyl2,6-dimethyl-5-phenyl-4-oxonicotinate.

Part B

4.0 g. of ethyl 2,6-dimethyl-5-phenyl-4-oxonicotinate was suspended in40 g. of 5% aqueous NaOH solution and heated on a steambath for 2 hours.The mixture was cooled and acidified, yielding 3.2 g. of2,6-dimethyl-5-phenyl-4-oxonicotinic acid. Recrystallization frommethanol provided material with a melting point of 272°-273° C.(decomposition).

Example 86A

1.53 g. of 2,6-dimethyl-5-phenyl-4-oxonicotinic acid, 0.23 g. of NaOHand 50 ml. of methanol were mixed. Evaporation of the solvent provided1.53 g. of sodium 2,6-dimethyl-5-phenyl-4-oxonicotinate as a glassysold.

Example 87

Part A

42.9 g. of ethyl β-methylaminocrotonate, 25 g. of pyridine and 600 ml.of dry methylene chloride were mixed. 56.7 g. of 4-chlorophenylacetylchloride was added with stirring. Three hours later the reaction mixturewas poured into 300 ml. of water. The methylene chloride layer wasseparated and evaporated yielding 91 g. of crude ethyl3-oxo-4-(4'-chlorophenyl)-2-(methylaminoethylidene)butrate as a lightyellow oil.

Part B

59.16 g. of ethyl3-oxo-4-(4'-chlorophenyl)-2-(methylaminoethylidene)burtrate was heatedat 80°-85° C. with 48 g. of dimethylformamide dimethyl acetal, 100 ml.of dry dimethylformamide and 8 ml. of triethylamine. After 19 hours, themixture was cooled, poured into 1000 ml. of water, acidified with diluteHCl and extracted with methylene chloride. Evaporation of the solventprovided ethyl 1,2-dimethyl-5-(4'-chlorophenyl)-4-oxonicotinate as awhite solid. m.p=200°-201° C. (acetonitrile).

Example 88

Approximately 30 g. of ethyl1,2-dimethyl-5-(4'-chlorophenyl)-4-oxonicotinate was suspended in 300 g.of 5% aqueous NaOH solution. 300 ml. of methanol was added and themixture was refluxed for 7 hours. The resulting solution was cooled andacidified to yield 18.9 g. of1,2-dimethyl-5-(4'-chlorophenyl)-4-oxonicotinic acid as a white solid,m.p.=239°-240° C. (acetonitrile).

Example 88A

18.5 g. of 1,2-dimethyl-5-(4'-chlorophenyl)-4-oxonicotinic acid wasmixed with 2.93 g. of NaOH and 200 ml. of methanol. Evaporation of thesolvent provided 19.0 g. of sodium1,2-dimethyl-5-(4'-chlorophenyl)-4-oxonicotinate as a glassy solid.

Example 89

Part A

14.8 g. of ethyl3-oxo-4(4'-chlorophenyl)-2-(methylamino-ethylidene)butrate, 10 g. ofdimethylacetamide dimethyl acetal, 25 ml. of dry dimethylformamide and 2ml. of triethylamine were heated at 85° C. for 221/2 hours. The reactionwas cooled, poured into 400 ml. of water and extracted with methylenechloride. Evaporation of the solvent provided an oily residue of ethyl1,2,6-trimethyl-5-(4'-chlorophenyl)-4-oxonicotinate.

Part B

13.0 g. of crude ethyl1,2,6-trimethyl-5-(4'-chlorophenyl)-4-oxonicotinate was suspended in 130ml. of 5% NaOH in 1:1 methanol/water and refluxed for 6 hours. Thereaction mixture was cooled and acidified. Extraction of this materialwith methylene chloride provided 1.8 g. of1,2,6-trimethyl-5-(4'-chlorophenyl)-4-oxonicotinic acid. m.p.(acetonitrile) 240°-243° C.

Example 89A

1.8 g. of 1,2,6-trimethyl-5-(4'-chlorophenyl)-4-oxonicotinate, 0.27 g.of NaOH and 50 ml. of methanol were mixed. Evaporation of the solventprovided 1.9 g. of sodium1,2,6-trimethyl-5-(4'-chlorophenyl)-4-oxonicotinate as a glassy solid.

Example 90

Part A

24.6 g. of ethyl β-methylaminocrotonate was mixed with 250 ml. ofmethylene chloride and 16 ml. of pyridine. 40 g. of 4-bromophenylacetylchloride was added with stirring. 21/2 hours later, the reaction mixturewas poured into water. Separation of the organic layer provided 60.6 g.of ethyl 3-oxo-4-(4'-bromophenyl)-2-(methylamino-ethylidene)butrateafter evaporation.

Part B

17 g. of ethyl3-oxo-4-(4'-bromophenyl-2-(methylamino-ethylidene)butrate, 12 g. ofdimethylformamide dimethyl acetal, 25 ml. of dry dimethyl formamide and2 ml. of triethylamine were heated under dry nitrogen at 85° C. for 19hours. The reaction mixture was cooled, poured into 500 ml. of H₂ O,acidified with dilute HCl and extracted with methylene chloride.Evaporation of the solid provided 14.3 g. of crude ethyl1,2-dimethyl-5-(4'-bromophenyl)-4-oxonicotinate.

Part C

14.3 g. of ethyl 1,2-dimethyl-5-(4'-bromophenyl)-4-oxonicotinate wassuspended in 140 g. of 5% NaOH in 1:1 methanol/water and refluxed for41/2 hours. The reaction was cooled, diluted with water and acidified.The resulting solid was recrystallized from acetonitrile to yield 6.2 g.of 1,2-dimethyl-5-(4'-bromophenyl)-4-oxonicotinic acid as a white solid,m.p.-266°-268° C. (decomposition).

Example 90A

6.15 g. of 1,2-dimethyl-5-(4'-bromophenyl)-4-oxonicotinic acid was mixedwith 0.84 g. of NaOH and 100 ml. of dry methanol. Evaporation of thesolvent provided 6.7 g. of sodium1,2-dimethyl-5-(4'-bromophenyl)-4-oxonicotinate as a tan glassy solid.

Example 91

Part A

15.7 g. of ethyl 3-methylamino-hex-2-enoate, 175 ml. of dry methylenechloride and 10 ml. of pyridine were mixed. 23 g. of 4-bromophenylacetylchloride was added with stirring. Two hours later the reaction mixturewas poured into water and the organic layer was separated and evaporatedyielding 45 g. of ethyl3-oxo-4-(4'-bromophenyl)-2-(methylaminopropylmethylene)butrate as abrownish oil.

Part B

18.4 g. of3-oxo-4-(4'-bromophenyl)-2-(methylaminopropylmethylene)butrate was mixedwith 12 g. of dimethylformamide dimethyl acetal, 25 ml. of dry dimethylformamide, and 2 ml. of dry pyridine. The reaction was heated at 85° C.for 21 hours, then cooled, poured into water, acidified and extractedwith methylene chloride. Evaporation of the solvent provided 16.5 g. ofcrude ethyl 1-methyl-2-propyl-5-(4'-bromophenyl)-4-oxonicotinate.

Part C

16.5 g. of ethyl 1-methyl-2-propyl-5-(4'-bromophenyl)-4-oxonicotinatewas suspended in 160 g. of 5% NaOH in 1:1 methanol/water. The mixturewas refluxed for 10 hours, cooled and acidified. Filtration of theresulting solid provided 9.0 g. of1-methyl-2-propyl-5-(4'-bromophenyl)-4-oxonicotinic acid. m.p.(acetonitrile)-237°-239° C. (decomposition).

Example 91A

8.8 g. of 1-methyl-2-propyl-5-(4'-bromophenyl)-4-oxonicotinic acid wasmixed with 1.1 g. of NaOH and 100 ml. of methanol. Evaporation of thesolid provided 8.8 g. of sodium1-methyl-2-propyl-5-(4'-bromophenyl)-4-oxonicotinate as a glassy powder.

Example 93

Part A

17.0 g. of ethyl3-oxo-4-(4'-bromophenyl)-2-(methylamino-ethylidene)butrate was mixedwith 10 g. of dimethylacetamide dimethyl acetal, 25 g. of drydimethylformamide and 2 ml. of triethylamine. The reaction mixture washeated at 85° C. for 241/2 hours under a nitrogen atmosphere, cooled,poured into water, acidified and extracted with methylene chloride.Evaporation of the solvent and trituration of the residue with etherprovided 2.7 g. of crude ethyl1,2,6-trimethyl-5-(4'-bromophenyl)-4-oxonicotinate as a brownish solid.

Part B

2.7 g. of crude ethyl 1,2,6-trimethyl-5-(4'-bromophenyl)-4-oxonicotinatewas suspended in 27 g. of 5% NaOH in 1:1 methanol/water. The reactionmixture was refluxed for 21/2 hours, cooled and acidified. Filtration ofthe resulting solid provided 2.2 g of1,2,6-trimethyl-5-(4-bromophenyl)-4-oxonicotinic acid. m.p.=228°-230° C.(decomposition).

Example 93A

1.96 g. of 1,2,6-trimethyl-5-(4'-bromophenyl)-4-oxonicotinic acid, 0.26g. of NaOH and 30 ml. of methanol were mixed. Evaporation of the solventprovided 2.0 g. of sodium1,2,6-trimethyl-5-(4'-bromophenyl)-4-oxonicotinic acid as a tan glassysolid.

Example 94

Part A

18.4 g. of ethyl β-anilinocrotonate was mixed with 800 ml. of methylenechloride and 8 ml. of pyridine. 17.0 g. of 4-chlorophenyl acetylchloride was added with stirring. After 21/2 hours the reaction mixturewas poured into 400 ml. of water and shaken. The methylene chloridelayer was separated and evaporated yielding 32 g. of crude ethyl3-oxo-4-(4'-chlorophenyl)-2-(anilino-ethylidene)butrate as a light brownoil.

Part B

32 g. of ethyl 3-oxo-4-(4'-chlorophenyl)-2-(anilino-ethylidene)butrate,15.9 g. of dimethylformamide dimethyl acetal, 40 ml. of drydimethylformamide and 3.5 ml. of triethylamine were mixed and heatedunder nitrogen at 80°-85° C. for 18 hours. The reaction was cooled,poured into 600 ml. of water, acidified and extracted with methylenechloride. Evaporation of the solvent provided 35 g. of crude ethyl2-methyl-1-phenyl-5-(4'-chlorophenyl)-4-oxonicotinate as a brown oil.

Part C

35 g. of crude ethyl2-methyl-1-phenyl-5-(4'-chlorophenyl)-4-oxonicotinate was suspended in350 g. of 5% NaOH in 1:1 methanol/water and refluxed for 6 hours. Thereaction mixture was cooled. This yielded a precipitate of sodium2-methyl-1-phenyl-5-(4'-chlorophenyl)-4-oxonicotinate which wascollected by filtration and resuspended in dilute aqueous HCl to provide5.3 g. of 2-methyl-1-phenyl-5-(4'-chlorophenyl)-4-oxonicotinic acid,m.p. (acetonitrile)-209°-209° C.

Example 94A

5.25 g. of 2-methyl-1-phenyl-5-(4'-chlorophenyl)-4-oxonicotinic acid,0.68 g. of NaOH and 100 g. of dry methanol were mixed. Evaporation ofthe solvent provided 5.0 g. of sodium2-methyl-1-phenyl-5-(4'-chlorophenyl)-4-oxonicotinate as a glassy solid.

D. N-alkyl-2,6-diaryl-4-oxonicotinates

In still another preferred aspect, this invention relates to compoundsof the formula: ##STR36## wherein R₁ is a (C₁ -C₆)alkyl group; R₅ is ahydrogen atom, a (C₁ -C₄)alkyl group or a halogen atom; Y is a hydrogenatom or a (C₁ -C₆)alkyl group; X is a hydrogen atom, a halogen atom, atrihalomethyl group, a (C₁ -C₆)alkyl group, a nitro group, a cyano groupor a (C₁ -C₆)alkoxy group; n is the integer 1 or 2; and theagronomically acceptable salts thereof.

Among the preferred compounds of the present invention are compounds ofGroup D, formula (XXXII) wherein R₁ is a (C₁ -C₆)alkyl, (C₁-C₄)haloalkyl, alkoxy(C₁ -C₄)alkyl(C₁ -C₄), aryl(C₆ -C₁₀)alkyl(C₁ -C₄),or (C₃ -C₆)alkenyl; Y is hydrogen, (C₁ -C₆)alkyl, an alkali or alkalineearth metal cation, or an ammonium or mono-, di-, tri-, or quaternaryammonium cation; R₅ is hydrogen, (C₁ -C₆)alkyl, or halogen; X ishydrogen, halogen, trihalomethyl, (C₁ -C₆)alkyl, (C₁ -C₆)alkoxy, nitroor cyano; and n is an integer from 1 to 2.

Among the more preferred compounds of the present invention arecompounds of Group D, Formula (XXXII) wherein R₁ is (C₁ -C₃)alkyl; R₅ ishydrogen or bromine; Y is hydrogen, sodium or potassium; X is hydrogenor halogen; is an integer 1 or 2.

Among the most preferred compounds of this invention are compounds ofGroup D Formula (XXXII) wherein R₁ is methyl or ethyl; R₅ is a hydrogenatom; and Y is hydrogen or a sodium or potassium cation; X is hydrogen,chlorine or fluorine; and n is 1; and the agronomically acceptable acidaddition salts thereof.

Typical compounds encompassed by the present invention include:

1-methyl-2,6-diphenyl-4-oxonicotinic acid;

1-propyl-2,6-diphenyl-4-oxonicotinic acid;

1-hexyl-2,6-diphenyl-4-oxonicotinic acid;

5-bromo-1-methyl-2,6-diphenyl-4-oxonicotinic acid;

5-chloro-1-ethyl-2,6-diphenyl-4-oxonicotinic acid;

1,5-dimethyl-2,6-diphenyl-4-oxonicotinic acid;

1-methyl-2,6-di(4'-chlorophenyl)-4-oxonicotinic acid;

1-butyl-2,6-di(4'-chlorophenyl)-4-oxonicotinic acid;

1-ethyl-2,6-di(3'-chlorophenyl)-4-oxonicotinic acid;

1-methyl-2,6-di(2'-chlorophenyl)-4-oxonicotinic acid;

1-methyl-2,6-di(4'-fluorophenyl)-4-oxonicotinic acid;

1-methyl-2,6-di(3'-fluorophenyl)-4-oxonicotinic acid;

5-bromo-1-methyl-2,6-di(4'-fluorophenyl-4-oxonicotinic acid;

1-ethyl-2,6-di(3',4'-dichlorophenyl)-4-oxonicotinic acid;

1-propyl-2,6-di(2',4'-dichlorophenyl)-4-oxonicotinic acid;

1-methyl-2,6-di(4'-trifluorophenyl)-4-oxonicotinic acid;

1-methyl-2-(4'-fluorophenyl)-6-phenyl-4-oxonicotinic acid;

1-methyl-2-(4'-chlorophenyl)-6-(4'-fluorophenyl)-4-oxonicotinic acid;

1-chloro-2-(4'-chlorophenyl)-6-phenyl-4-oxonicotinic acid;

1-pentyl-6-(4'-fluorophenyl)-2-phenyl-4-oxonicotinic acid;

and the agronomically acceptable salts thereof.

The compounds of the present invention can be prepared by varioussynthetic routes found in the art. In particular, the compounds of thepresent invention can be prepared by the following reaction sequence:##STR37## Another route to the compounds of Group D, formula (XXXII) is:##STR38##

Still another route to the compounds of Group D, formula (XXXII) of thepresent invention is shown by the following reaction sequence: ##STR39##

Yet another route to the compounds of Group D, formula (XXXII) of thepresent invention is shown by the following reaction equation: ##STR40##

Tables VIII and IX below are presented to illustrate the more preferredcompounds of this aspect of the present invention and related compoundsand the analytical data for these compounds.

                  TABLE VIII                                                      ______________________________________                                        List of Group D Compounds                                                      ##STR41##                  (XXXII)                                           Example No.                                                                             R.sub.1  R.sub.5                                                                             X        X'    Y                                     ______________________________________                                         97       H        H     H        H     H                                      97a      H        H     H        H     Na                                     98       Me       H     H        H     Et                                     99       Me       H     H        H     Me                                    100       Me       H     H        H     H                                      100a     Me       H     H        H     Na                                    101       Et       H     H        H     H                                      101a     Et       H     H        H     Na                                    102       Me       H     4-Br     4-Br  H                                      102a     Me       H     4-Br     4-Br  Na                                    103       Me       H     4-Br     4-Br  Et                                    104       Me       H     4-F      4-F   H                                      104a     Me       H     4-F      4-F   Na                                    105       Me       H     4-Cl     4-Cl  H                                      105a     Me       H     4-Cl     4-Cl  Na                                    106       Me       H     4-CH.sub.3                                                                             4-CH.sub.3                                                                          H                                      106a     Me       H     4-CH.sub.3                                                                             4-CH.sub.3                                                                          Na                                    107       Me       H     H        4-CH.sub.3                                                                          H                                      107a     Me       H     H        4-CH.sub.3                                                                          Na                                    108       Me       Br    H        H     H                                      108a     Me       Br    H        H     Na                                    109       Pr       H     H        H     H                                      109a     Pr       H     H        H     Na                                    ______________________________________                                    

                  TABLE IX                                                        ______________________________________                                        Example No. mp (°C.)                                                                        % C       % H  % N                                       ______________________________________                                         97         228-230  74.21     4.50 4.80                                                           74.46     4.40 5.15                                       97a        --       --        --   --                                         98         177-179  75-65     5.74 4.20                                                           75.49     5.83 4.45                                       99         255-257  75.22     5.37 4.39                                                           75.13     5.51 4.46                                      100         209-211  74.74     4.95 4.59                                                           74.04     5.04 4.47                                       100a       --       --        --   --                                        101         210-213  75.22     5.37 4.39                                                           75.28     5.37 4.22                                       101a       --       --        --   --                                        102         197      49.27     2.83 3.03                                                           49.27     2.86 3.34                                       102a       --       --        --   --                                        103         218-220  51.35     3.49 2.85                                                           50.45     3.43 3.03                                      104         191-193  66.86     3.84 4.10                                                           58.41     3.67 4.25                                       104a       --       --        --   --                                        105         187-190  60.98     3.50 3.74                                                           60.75     3.53 4.29                                       105a       --       --        --   --                                        106         209-212  75.65     5.74 4.20                                                           74.89     5.79 4.26                                       106a       --       --        --   --                                        107         158-163  75.22     5.37 4.39                                                           72.13     5.50 4.02                                       107a       --       --        --   --                                        108         242-243  59.39     3.67 3.65                                                           60.44     3.77 4.15                                       108a       --       --        --   --                                        109         166.7    75.20     6.31 4.18                                                           75.14     5.85 4.28                                       109a       --       --        --   --                                        ______________________________________                                    

EXPERIMENTAL PROCEDURES Example 98

Part a:

A 500 ml single neck flask was fitted with a magnetic stirrer and an N₂inlet. 20 gms of ethyl benzoylacetate (0.104 moles) was dissolved in 200gms of 1:10 P₂ O₅ /methanesulfonic acid and added to the flask. Thehomogeneous reaction mixture was heated to 40° and maintained at thattemperature for four days. The mixture was then cooled and diluted with100 mls of methylene chloride. This solution was added in 50 ml portionsto 1000 mls of cold water in a separatory funnel. The separatory funnelwas shaken vigorously after each addition. The organic layer was thenwashed with water and evaporated leaving an oily residue thatcrystallized from ether. The isolated yield of2,6-diphenyl-3-ethoxycarbonyl-4-pyrone was 10.5 gms (63%). mp=102°-3°

Part b:

3.5 gms of 2,6-diphenyl-3-ethoxycarbonyl-4-pyrone was dissolved in 33mls of methanol. 2 mls of glacial acetic acid was added. 13.3 mls of 40%aqueous methylamine was then added very slowly at room temperature.After 6 hours the reaction mixture was diluted with 200 mls of water andextracted with methylene chloride. Evaporation yielded 3.5 gms of ethyl2,6-diphenyl-1-methyl-4-oxonicotinate which was recrystallized frommethylene chloride/ether. mp=177°-9°

Example 99

Part a:

A 200 ml flask was fitted with a N₂ inlet, a magnetic stirring bar and acondenser. 50 mls of methanol, 8.0 gms of trimethyl orthoformate, 5.2gms of concentrated H₂ SO₄ and 5.0 gms of3-benzoyl-4-hydroxy-6-phenyl-pyr-2-one were added. The resulting mixturewas then refluxed for 3 days, cooled, poured into water and extractedwith methylene chloride (300 mls). The organic extracts were combinedand washed with water. Removal of the solvent provided 4.4 gms of2,6-diphenyl-3-methoxy-carbonyl-pyr-4-one (85%). Recrystallization frommethylene chloride/ether provide material with a melting point=150°-1°.

Part b:

3.0 gms of 2,6-diphenyl-3-methoxycarbonyl-pyr-4-one, 33 mls of methanol,13.3 mls of 40% aqueous methylamine and 2 mls of glacial acetic acidwere mixed at room termperature. The next day the mixture was dilutedwith water. Filtration of the resulting suspension yielded 2.5 gms ofmethyl 2,6-diphenyl-1-methyl-4-oxonicotinate. Recrystallization frommethanol provided material at 255°-7°.

Example 100

2.5 gms of methyl 2,6-diphenyl-1-methyl-4-oxonicotinate was suspended in28 mls of 5% aqueous sodium hydroxide 8 hours, cooled, and filtered toremove residual insolubles. The clear basic solution was then acidifiedwith dilute HCl to provide a white precipitate of2,6-diphenyl-1-methyl-4-oxonicotinic acid. Recrystallization frommethylene chloride/ether provided 2.4 gms of product. mp=209°-11° (dec).

Example 100a

1.73 gms of 2,6-diphenyl-1-methyl-4-oxonicotinic acid was suspended in50 mls of dry methanol. 0.25 gms of NaOH was added. After the carboxylicacid and the NaOH dissolved the solvent was removed yielding 1.75 gms ofsodium 2,6-diphenyl-1-methyl-4-oxonicotinate as a glassy solid.

Example 101

3.5 gms of 2,6-diphenyl-3-ethoxycarbonyl-pyr-4-one, 33 mls of methanol,5 mls of water and 2 mls of glacial acetic acid were mixed. 7.6 mls of70% aqueous ethylamine was then added slowly and the resulting mixturewas allowed to stand at room temperature for 24 hours. The mixture wasthen diluted with 100 mls of water. The pH was adjusted to 2. Extractionwith methylene chloride and evaporation of the solvent provided 3.0 gmsof crude ethyl 1-ethyl-2,6-diphenyl-4-oxonicotinate as a brown oil. Thismaterial was dissolved in 20 mls of methanol. This solution was thenadded to 40 mls of 5% aqueous NaOH and heated on a steambath for 5hours. The reaction mixture was cooled and acidified. Extraction withmethylene chloride (3×50 mls) yielded an oily solid after evaporation.Crystallization from methylene chloride/ether yielded 1.6 gms of1-ethyl-2,6-diphenyl-4-oxonicotinic acid. mp=210°-3° (dec).

Example 101a

1.38 gms of 1-ethyl-2,6-diphenyl-4-oxonicotinic acid was treated with0.19 gms of NaOH in 50 mls of dry methanol. Evaporation of the solventprovided 1.40 gms of sodium 1-ethyl-2,6-diphenyl-4-oxonicotinate as aglassy solid.

Example 104

Part a:

25 gms of ethyl 4-fluorobenzoylacetate was dissolved in 250 gms of 1:10P₂ O₅ /methanesulfonic acid and heated at 45° for 4 days. The mixturewas cooled, poured into 1200 mls of water and extracted with (3×100 mls)methylene chloride. Evaporation of the solvent and chromatography of theresulting oil (silica gel/ether) provided 12.9 gms of crystalline2,6-di(4'-fluorophenyl)-3-ethoxycarbonyl-pyr-4-one. mp=113-4.

Part b:

5 gms of 2,6-di(4'-fluorophenyl)-3-ethoxycarbonyl-pyr-4-one, 47 mls ofmethanol and 2.9 mls of glacial acetic acid were mixed. 19 mls of 40%aqueous methylamine was added slowly. Three hours later the reactionmixture was poured into 200 mls of water and extracted with methylenechloride (2×100 mls). This provided 5.4 gms of crude ethyl1-methyl-2,6-di(4'-fluorophenyl)-4-oxonicotinate as a brown oil.

The crude ester was suspended in 50 mls of 5% aqueous NaOH solution andheated for 3 hours. The mixture was cooled and acidified. Extractionwith methylene chloride provided a yellow solid which was recrystallizedfrom methylene chloride/ether to provide 3.6 gms of1-methyl-2,6-di(4'-fluorophenyl)-4-oxonicotinic acid. mp=191°-3°

Example 104a

3.45 gms of 1-methyl-2,6-di(4'-fluorophenyl)-4-oxonicotinic acid wasmixed with 0.445 gms of NaOH and 70 mls of methanol. Evaporation of thesolvent provided 3.1 gms of sodium1-methyl-2,6-di(4'-fluorophenyl)-4-oxonicotinate as a glassy solid.

Example 105

Part a:

15 gms of ethyl 4-chlorobenzoylacetate was mixed with 150 gms of 1:10 P₂O₅ /methanesulfonic acid and heated at 45° for 4 days. The cooledreaction mixture was poured into a separatory funnel containing 1500 mlsof cold water and the resulting mixture was shaken for several minutes.Extraction with methylene chloride and chromatograph, of the resultingcrude product (silica gel/ether) provided 5.5 gms of ethyl2,6-di(4'-chlorophenyl)-3-ethoxycarbonyl-pyr-4-one. mp=130°.

Part b:

5.0 gms of ethyl 2,6-di(4'-chlorophenyl)3-etoxycarbonyl-pyr-4-one, 100mls of methanol, 19 mls of 40% aqueous methylamine, 19 mls of water and2.9 mls of glacial acetic acid were mixed and allowed to stand at roomtemperature for 3 hours. The mixture was poured into water and extractedwith methylene chloride to provide 5 gms of crude ethyl1-methyl-2,6-di(4-chlorophenyl)-4-oxonicotinate as a yellowishsemi-solid.

The ester was then suspended in 50 mls of 5% aqueous NaOH solution. 20mls of methanol was added to improve solubility. The mixture was heatedon a steambath for 3 hours, cooled, and acidified with dilute HCI toprovide a white precipitate. Recrystallization from methylenechloride/ether, yielded 3.4 gms of1-methyl-2,6-di(4'-chlorophenyl)-4-oxonicotinic acid. mp=187°-90°

Example 105a

3.32 gms of 1-methyl-2,6-di(4'-chlorophenyl)-4-oxonicotinic acid, 0.39gms of NaOH and 50 mls of methanol were mixed. Evaporation of thesolvent provided 3.4 gms of sodium1-methyl-2,6-di(4'-chlorophenyl)-4-oxonicotinate as a glass solid.

Example 107

Part a:

A one liter flask was fitted with a mechanical stirrer, CaCl₂ dryingtube, condenser and a sidearm addition funnel. 100 gms of PCl₅ wasplaced in the flask. 39 gms of ethyl 4-methylbenzoylacetate and 100 gmsof PCl₃ were mixed and slowly added to the PCl₅ at room temperature. Thereaction mixture evolved HCl. After 30 minutes the mixture wascautiously refluxed for 2 hours. At this time PCl₃ and POCl₃ weredistilled from the reaction mixture at reduced pressure. The residue wasthen distilled at 0.5 mm (bp=116°-121°) to provide 32 gms of-chloro-4-methylcinnamoyl chloride as a clear oil.

Part b:

10.0 gms of ethyl B-methylaminocinnamate, 9.6 gms of pyridine and 75 mlsof dry methylene chloride were mixed in a flask under a dry nitrogenatmosphere. 10 gms of β-chloro-4-methylcinnamoyl chloride in 25 mls ofmethylene chloride were added at ambient temperatures. After 2 hours thereaction mixture was poured into water and extracted with methylenechloride. Evaporation of the solvent provided 18 gms of a brown oil.This material was heated (160°-178°) for 15 minutes (HCl evolution),cooled, and taken up in dilute aqueous NaOH. Acidification of the basicextracts and recrystallization of the resulting solid from methanolprovided 0.8 gms of 1-methyl-2-phenyl-6-(4'-methylphenyl)-4-oxonicotinicacid. mp=158-63 (dec).

Example 107a

0.64 gms of 1-methyl-2-phenyl-6-(4'-methylphenyl)-4-oxonicotinic acid,0.09 gms of NaOH and 30 mls of methanol were mixed. Evaporation of thesolvent provided 0.6 gms of sodium1-methyl-2-phenyl-6-(4'-methylphenyl)-4-oxonicotinate as a glassy solid.

Example 108

3.75 gms of 1-methyl-2,6-diphenyl-4-oxonicotinic acid was dissolved in40 mls of methanol. The pH was adjusted to 12 with the addition ofaqueous NaOH. A methanolic solution of bromine (2.95 gms Br₂ in 50 mlsmethanol) was added. Additional NaOH was added as required to maintain abasic medium. Removal of the solvent yielded a semi-solid that was takenup in 100 mls of water. Water insoluble material was removed byfiltration. Acidification of the aqueous solution provided 3.0 gms of5-bromo-1-methyl-2,6-diphenyl-4-oxonicotinic acid (mp 242°-3°, withdecomposition) as a white solid.

Example 108a

2.5 gms of 5-bromo-1-methyl-2,6-diphenyl-4-oxonicotinic acid, 0.286 gmsof NaOH and 50 mls of dry methanol were mixed. Evaporation of thesolvent provided 2.6 gms of sodium5-bromo-1-methyl-2,6-diphenyl-4-oxonicotinate as a tan glassy solid.

Example 109

4.0 gms of 2,6-diphenyl-3-ethoxycarbonyl-pyr-4-one, 50 mls of glacialacetic acid were mixed. 8.1 gms of n-propylamine and 6 mls of water wasadded slowly at room temperature. After 3 hours an additional 14 mls ofwater, 12 mls of 6% HCl and enough methanol to bring everything intosolution, was added. The next day this acidic reaction misture waspoured into water and extracted with methylene chloride (2×100 mls).Evaporation of the organic extracts yield 4.4 gms of crude nicotinateester which was suspended in 50 mls of 5% aqueous NaOH and heated at 85°for 4 hours. The resulting solution was acidified with HCl and extractedwith methylene chloride (2×50 mls). Evaporation of the solvent yielded asolid mass. Recrystallization from ether provided 1.5 gms of1-propyl-2,6-diphenyl-4-oxonicotinic acid. mp=166°-7°.

Example 109a

1.5 gms of 1-propyl-2,6-diphenyl-4-oxonicotinic acid, 0.202 gms of NaOHand 50 mls of dry methanol were mixed. Evaporation of the solventyielded 1.5 gms of sodium 1-propyl-2,6-diphenyl-4-oxonicotinate as awhite glassy solid.

The compounds of the invention are particularly useful as chemicalhybridization agents in cereal crops, such as wheat, barley, corn, rice,sorghum, millets, oats, rye, triticale and the like. When used aschemical hybridization agents, the compounds effectively induce a highdegree of selective male sterility, that is, without also inducingsignificant female sterility, in the treated plants and without cuasingsignificant growth inhibition of the treated plants. As used herein, theterm male sterility includes both actual male sterility, as evidenced bya lack of male flower parts or by sterile pollen, and functional malesterility, in which the male flower parts are unable to causepollination. The compounds of the invention also cause other plantgrowth regulatory responses, such as for example, control of flowering,control of fruiting and inhibition of seed formation in non-cerealspecies and other related growth regulatory responses.

When used as plant growth regulators, the compounds of the invention areapplied in any amount which will be sufficient to effect the desiredplant response without causing any undesirable or phytotoxic response.For example, when the compounds of the invention are used as chemicalhybridization agents, they are generally applied to the crops to betreated at a rate of about 1/32 to about 20 pounds per acre andpreferably about 1/8 to about 10 pounds per acre. The rate ofapplication will vary depending on the crop being treated, the compoundbeing used for treatment, and related factors.

To obtain hydrid seed, the following procedure is generally employed.The two parents to be crossed are planted in alternate strips. Thefemale parent is treated with a compound of the invention. Themale-sterile female parent thus produced will be pollinated by pollenfrom the other, male-fertile, male parent, and the seed produced by thefemale parent will be hybrid seed which can then be harvested byconventional means.

A preferred method of applying a compound of the invention as a chemicalhybridization agent is by foliar application. When this method isemployed, selective male sterility is most effectively induced when thecompound is applied between another initiation and meiosis. Thecompounds of the inventions may also be applied as a seed treatment bysoaking the seed in a liquid formulation containing the active compoundor by coating the seed with the compound. In seed treatmentapplications, the compounds of the invention will generally be appliedat a rate of about 1/4 to about 10 pounds per hundred weight of seed.The compounds of the invention are also effective when applied to thesoil or to the water surface in rice crops.

The compounds of the invention can be used as plant growth regulatorseither individually or in mixtures. For example, they can be used incombination with other plant growth regulators, such as auxins,gibberellins, ethylene-releasing agents such as ethephon, pyridones,pyridazinones, cytokinins, maleic hydrazide, succinic acid2,2-dimethylhydrazide, chlorine and its salts(2-chloroethyl)trimethylammonium chloride, triiodobenzoic acid,tributyl-2,4-dichlorobenzylphosphonium chloride, polymericN-vinyl-2-oxazolidinones, tri)dimethylaminoethyl)phosphate and itssalts, and N-dimethylamino-1,2,3,6-tetrahydrophthalamic acid and itssalts, and the like, and under some conditions may be usedadvantageously with other agricultural chemicals such as herbicides,fungicides, insecticides, and plant bactericides.

A compound of the invention can be applied to the growth medium or toplants to be treated either by itself or, as is generally done, as acomponent in a growth regulant composition or formulation which alsocomprises an agronomically acceptable carrier. By "agronomicallyacceptable carrier" is meant any substance which can be used todissolve, disperse, or diffuse a compound in the composition withoutimpairing the effectiveness of the compound and which by itself has nosignificant detrimental effect on the soil, equipment, crops oragronomic environment. Mixtures of the compounds of the invention mayalso be used in any of these formulations. The compositions of theinvention can be either solid or liquid formulations or solutions. Forexample, the compounds can be formulated as wettable powders,emulsifiable concentrates, dusts, granular formulations, aerosols, orflowable emulsion concentrates. In such formulations, the compounds areextended with a liquid or solid carrier and, when desired suitablesurfactants are incorporated.

It is usually desirable, particularly in foliar applications, to includeadjuvants, such as wetting agents, spreading agents, dispersing agents,stickers, adhesives, and the like, in accordance with agriculturalpractices. Examples of adjuvants which are commonly used in the art canbe found in the John W. McCutcheon, Inc. publication "Detergents andEmulsifiers Annual".

The compounds of the invention can be dissolved in any appropriatesolvent. Examples of solvents which are useful in the practice of thisinvention include water, alcohols, ketones, aromatic hydrocarbons,halogenated hydrocarbons, dimethylformamide, dioxane, dimethylsulfoxide, and the like. Mixtures of these solvents can vary from about2% to about 98% by weight with a preferred range being from about 20% toabout 75%.

For the preparation of emulsifiable concentrates, the compound can bedissolved in organic solvents, such as benzene, toluene, xylene,methylated naphthalene, corn oil, pine oil, o-dichlorobenzene,isophorone, cyclohexanone, methyl oleate, and the like, or in mixturesof these solvents, together with an emulsifying agent or surfactantwhich permits dispersion in water. Suitable emulsifiers include, forexample, the ethylene oxide derivatives of alkylphenols or long-chainalcohols, mercaptans, carboxylic acids, and reactive amines andpartially esterified polyhydric alcohols. Solvent-soluble sulfates orsulfonates, such as the alkaline earth salts or amine salts ofalkyl-benzenesulfonates and the fatty alcohol sodium sulfates, havingsurface-active properties can be used as emulsifiers either alone or inconjunction with any ethylene oxide reaction product. Flowable emulsionconcentrates are formulated similarly to the emulsifiable concentratesand include, in addition to the above components, water and astabilizing agent such as a water-soluble cellulose derivative or awater-soluble salt of a polyacrylic acid. The concentration of theactive ingredient in emulsifiable concentrates of usually abut 10% to60% by weight and in flowable emulsion concentrates, this can be as highas about 75%.

Wettable powders suitable for spraying, can be prepared by admixing thecompound with a finely divided solid, such as clays, inorganic silicatesand carbonates, and silicas and incorporating wetting agents, stickingagents, and/or dispersing agents in such mixtures. The concentration ofactive ingredients in such formulations is usually in the range of about20% to 98% by weight, preferably, about 40% to 75%. A dispersing agentmay generally constitute about 0.5% to about 3% by weight of thecomposition, and a wetting agent may generally constitute from about0.1% to about 5% by weight of the composition.

Dusts can be prepared by mixing the compounds of the invention withfinely divided inert solids which may be organic or inorganic in nature.Materials useful for this purpose include, for example, botanicalflours, silicas, silicates, carbonates and clays. One convenient methodof preparing a dust is to dilute a wettable powder with a finely dividedcarrier. Dust concentrates containing abut 20% to 80% of the activeingredient are commonly made and are subsequently diluted to about 1% to10% by weight use concentration.

Granular formulations can be prepared by impregnating a solid such asgranular Fuller's earth, vermiculite, ground corn cobs, seed hulls,including bran or other grain hulls, or similar material. A solution ofone or more of the compounds in a volatile organic solvent can besprayed or mixed with the granular solid and the solvent then removed byevaporation. The granular material can have any suitable size, with apreferable size range of 16 to 60 mesh. The active compound will usuallycomprise about 2 to 15% by weight of the granular formulations.

Salts of the compounds of the invention can be formulated and applied asaqueous solutions. The salt will typically comprise about 0.05 to about50% by weight preferably about 0.1% to about 10%, of the solution.

These compositions can also be further diluted with water if desiredprior to actual application. In some applications, the activity of thesecompositions can be enhanced by incorporating into the composition anadjuvant such as glycerin, methylethylcellulose, hydroxyethylcellulose,polyoxyethylenesorbitan monooleate, polypropylene glycol, polyacrylicacid, polyethylene sodium malate, polyethylene oxide, or the like. Theadjuvant will generally comprise about 0.1 to about 5% by weight,preferably about 0.5 to about 2%, of the composition. Such compositionscan also optionally include an agronomically-acceptable surfactant.

The compounds of teh invention can be applied as sprays by methodscommonly employed, such as conventional hydraulic sprays, aerial sprays,and dusts. For low-volume applications, a solution of the compound isusually used. The dilution and volume of application will usually dependupon such factors as the type of equipment employed, the method ofapplication, the area to be treated and the type and stage ofdevelopment of the crop being treated.

The following is a typical tank mix formulation for the foliarapplication of sodium1-ethyl-6-methyl-2-(4-chlorophenyl)-4-oxonicotinate on winter wheat at arate of 0.25 lbs./A:

0.25 lbs. of oxonicotinate salt

1 pt. of Triton AG98®

dulute to 50 gals. with water

This mixture is then foliar spray-applied to the wheat plants at a rateof 50 gals./A.

The following examples will further illustrate the chemicalhybridization activity of the compounds of the invention but are notintended to limit the invention in any way.

Example 110 Chemical hybridization activity

The following procedures are used to evaluate the activity of thecompounds of the invention for inducing male sterility in cereals.

An awned variety (Fielder) and an awnless variety (Mayo-64) of springwheat are planted at the rate of 6 to 8 seeds per 6 inches potcontaining a sterile medium of 3 parts soil and 1 part humus. The plantsare grown under short-day (9 hour) conditions for the first 4 weeks toobtain good vegetative growth before flower initiation. The plants arethen moved to long-day (16 hour) conditions which are provided by highintensity lights in the greenhouse. The plants are fertilized at 2, 4,and 8 weeks after planting with a water soluble fertilizer (16-25-16) atthe rate of 1 tsp/gal of water, and are frequently sprayed with isotoxfor aphid control and dusted with sulfur for powdery mildew control.

Test compounds are foliarly applied to the awned female plants whenthese plants reach the flag leaf emergence stage (stage 8 on Feekes'scale). All compounds are applied in a carrier volume of 50 gal/Acontaining a surfactant, such as Triton X-100 at the rate of 20 oz/50gal.

After spike emergence but before anthesis, 4 to 6 spikes per pot arebagged to prevent outcrossing. At the first signs of flower opening, twospikes per pot are cross pollinated, using the approach method, with theawnless male parent. As soon as the seeds become plainly visible, spikelength is measured and seeds per spikelet counted in both bagged andcross spikes. Male sterility can then be calculated as percentinhibition of seed set in bagged spikes of treated plants, and femalefertility in crossed spikes can be calculated as percent of control seedset. After maturity the seed on crossed spikes are planted fordetermination of percent hybridization.

Percent sterility, percent fertility, and percent height inhibition arecalculated from the following formulas:

a.

% Sterility=(S_(c) -S₁ /S_(c))×100

S_(c) =seeds/spikelet in bagged spikes of control plants.

S_(t) =seeds/spikelet in bagged spikes of treated plants.

b.

% Fertility=(F_(t) /F_(c))×100

F_(t) =seeds/spikelet in approach crossed spikes of treated plants

F_(c) =seeds/spikelet in unbagged spikes of control plants

c.

% Height inhibition=(H_(c) -H_(t) /H_(c))×100

H_(c) =Height of control plants

H_(t) =Height of treated plants

Table III summarizes typical results obtained in the evaluation ofcompounds of the invention. A dash indicates that no determination ofvalue was made.

                  TABLE X                                                         ______________________________________                                        Biological Data (Wheat Greenhouse Data)                                       % Male Sterility at Dosage (lbs./A)                                           Exam-                                                                         ple #  8        4      2    1    1/2  1/4  1/8  1/64                          ______________________________________                                         1     not active at 8 lbs/A or below                                          2     not active at 8 lbs/A or below                                          3     not active at 8 lbs/A or below                                          4a    --       100    100  77   36   --   --                                  5     --       --     --   --   --   --   --                                  5a    100      --     100  --   43   --   2                                   6     --       --     --   --   --   --   --                                  6a    100      --     85   --   18   --   54                                  7     --       --     --   --   --   --   --                                  7a    not active at 8 lbs/A or below                                          8     --       --      --  --   --   --   --                                  8a    --       --     98   --   34   --   1                                   9     --       --     --   --   --   --   --                                  9a    99       --     88   --   32   --   5                                  10     --       --     --   --   --   --   --                                  10a   --       --     100  --   100  --   13                                 11     --       --     --   --   --   --   --                                  11a   --       88     --   2    --   2    --                                 12     --       --     --   --   --   --   --                                  12a   not active at 8 lbs/A or below                                         13     --       --     --   --   --   --   --                                  13a   --       100    100  92   55   12   --                                 14     not active at 8 lbs/A or below                                         15     not active at 8 lbs/A or below                                         16     --       --     --   --   --   --   --                                  16a   --       100    100  100  96   91   --                                 17     --       100    100  100  96   91   --                                  17a   100      --     100  18   0    --   0                                  18     --       --     --   --   --   --   --                                  18a   --       --     --   100  66   100  41                                 19     --       --     --   --   --   --   --                                  19a   not active at 8 lbs/A or below                                         20     --       --     --   --   --   --   --                                  20a   not active at 8 lbs/A or below                                         21     --       --     --   --   --   --   --                                  21a   not active at 8 lbs/A or below                                         22     --       --     --   --   --   --   --                                  22a   100      --     --   --   --   --   --                                 23     --       --     --   --   --   --   --                                  23a   not active at 8 lbs/A or below                                         24     --       --     --   --   --   --   --                                  24a   10       --     8    --   19   --   15                                 25     --       --     --   --   --   --   --                                  25a   --       55     49   0    0    0    --                                 26     --       --     --   --   --   --   --                                  26a   --       94     7    15   0    2    --                                 27     --       --     --   --   --   --   --                                  27a   --       100    100  57   0    2    --                                 28     --       --     --   --   --   --   --                                  28a   --       100    100  100  39   7    0                                  29     --       --     --   --   --   --   --                                  29a   --       100    70   1    0    0    --                                 30     --       --     --   --   --   --   --                                  30a   --       100    100  100  0    0    --                                 31     22       --     21   --   16   --   21                                 32     --       --     --   --   --   --   --                                  32a   --       100    100  100  100  87   --                                 33     --       --     --   --   --   --   --                                  33a   100      --     100  --   100  --   37                                 34     --       --     --   --   --   --   --                                  34a   100      --     79   --   50   --   44                                 35     --       --     --   --   --   --   --                                  35a   not active at or below 8 lbs/A                                         36     --       --     --   --   --   --   --                                  36a   100      --     100  --   13   --   1                                  37     --       --     --   --   --   --   --                                  37a   --       --     --   90   57   --   --                                 38     --       --     --   --   --   --   --                                  38a   --       --     --   100  65   0    0                                  39     --       --     --   --   --   --   --                                  39a   100      --     100  --   45   --   0                                  40     --       --     --   --   --   --   --                                  40a   100      --     92   --   14   --   0                                  41     not active at or below 8 lbs/A                                         42     --       --     --   --   --   --   --                                  42a   100      --     100  --   90   --   43                                 43     --       --     --   --   --   --   --                                  43a   100      --     100  --   100  --   100                                44     --       --     --   --   --   --   --                                  44a   100      --     100  --   80   --   4                                  45     --       --     --   --   --   --   --                                  45a   100      --     100  --   93   --   8                                  46     --       --     --   --   --   --   --                                  46a   100      --     100  --   73   --   0                                  47     --       --     --   --   --   --   --                                  47a   100      --     84   --   0    --   0                                  48     92       --     21   --   6    --   1                                  49     100      --     92   --   0    --   0                                  50     --       100    100  61   0    --   --                                 51     92       --     7    --   0    --   0                                  52     100      --     100  --   39   --   0                                  53     11.1     --     9.4  --   0    --   0                                  54     No heads --     100  --   44.6 --   13.6                               55     15.4     --     9.2  --   2.2  --   0                                  56     100      --     14   --   0    --   0                                  57     100      --     87.0 --   38.6 --   28.3                               58     100      --     94.6 --   48.9 --   0                                  59     100      --     100  --   56.5 --   9.0                                60     2.2      --     3.6  --   10.8 --   4.0                                61     13.9     --     9.9  --   0    --   9.4                                62     97.4     --     24.1 --   16.7 --   22.4                               63     35.1     --     6.1  --   8.3  --   18.9                               64     100      --     100  --   65.7 --   8.3                                65     --       --     34.3 --   9.9  --   24.4                               66     4.7      --     0    --   0    --   0                                  67     93.2     --     51.7 --   05.6 --   3.4                                68     0        --     10.7 --   12.4 --   0                                  69     48.8     --     51.2 --   20.3 --   68                                 70     26.6     --     15.2 --   22.8 --   32.3                               71     100      --     57.7 --   13.2 --   0                                  72     14.5     --     19.4 --   25   --   16                                 73     0        --     0    --   0    --   0                                  74     19.8     --     16.0 --   19.8 --   19                                 (32 lb/A-0% 8 lb/A-2.5% 2 lb/A-5.8%)                                          (16 lb/A-6.2% 4 lb/A-0%                                                       75     43.3     --     16.7 --   5.7  --   14.8                               76     100      --     97.7 --   65.0 --   16.0                               77     --       --     --   --   --   --   --                                 78     90.9     --     21.9 --   26.0 --   22.3                               79     0        --     0    --   3    --   3                                  80     --       --     --   --   --   --   --                                  80a   5        --     0    --   2    --   3                                  81     --       --     --   --   --   --   --                                  81a   --       7      5    5    5    5    5                                  82     0        --     0    --   0    --   --                                 83     --       --     --   --   --   --   --                                  83a   42       --     19   --   3    --   0                                  84     --       --     --   --   --   --   --                                  84a   12       --     --   --   --   --   --                                 85     --       --     --   --   --   --   --                                  85a   69       --     22   --   0    --   0                                  86     --       --     --   --   --   --   --                                  86a   0        --     0    --   0    --   0                                  87     99       --     90   --   63   --   28                                 88     --       --     --   --   --   --   --                                  88a   100      --     98   --   80   --   57                                 89     --       --     --   --   --   --   --                                  89a   100      --     100  --   100  --   100                                90     --       --     --   --   --   --   --                                  90a   100      --     100  --   44   --   35                                 91     --       --     --   --   --   --   --                                  91a   98       --     60   --   24   --   17                                 92     --       --     --   --   --   --   --                                  92a   66       --     16   --   8    --   3                                  93     --       --     --   --   --   --   --                                  93a   --       --     100  --   100  --   100  100                           94     --       --     --   --   --   --   --   --                             94a   39       --     1    --   7    --   1    --                            95     2        --     2    --   0    --   0    --                            96     --       --     --   --   --   --   --   --                             96a   0        --     0    0    0    --   0    --                            97     --       --     --   --   --   --   --                                  97a   0        --     0    --   0    --   0                                  98     16       --     0    --   4    --   9                                  99     10       --     --   --   --   --   --                                 100    --       --     --   --   --   --   --                                 100a   --       100    100  88   10   --   --                                 101    --       --     --   --   --   --   --                                 101a   100      --     81   --   6    --   0                                  102a   0        0      2    --   --   --   --                                 103    1        --     0    --   0    --   0                                  104    --       --     --   --   --   --   --                                 104a   --       100    100  91   56   66   --                                 105    --       --     --   --   --   --   --                                 105a   --       100    100  97   18   11   --                                 106    --       --     --   --   --   --   --                                 106a   0        --     6    --   0    --   4                                  107    --       --     --   --   --   --   --                                 107a   32       --     0    --   0    --   0                                  108    --       --     --   --   --   --   --                                 108a   --       --     78   --   11   --   2                                  109    --       --     --   --   --   --   --                                 109a   --       --     73   --   14.2 --   0                                  ______________________________________                                    

Table XI below depicts the male/female selectivity of several of thecompounds of Group A, formula II, of the present invention. Applicationrates sufficient to effect high levels of male sterility maintain highlevels of female fertility. Substantial loss of female fertility occursonly at overdose application rates

                  TABLE XI                                                        ______________________________________                                        Female Fertility, Culm Inhibition, Height Inhibition                          (Wheat Greenhouse Data)                                                               Dosage  %        % Culm % Spike                                                                              % Female                               Example #                                                                             (lbs/A) Sterility                                                                              Inhibition                                                                           Inhibition                                                                           Fertility                              ______________________________________                                        13a     1       100      15     23     --                                             1/2      93      5      9      23                                             1/4     100      0      0      67                                             1/8      98      0      11     80                                             1/16     10      0      0      --                                     16a     1       100      50     28     --                                             1/2     100      40     14     --                                             1/4     100      20     14     --                                             1/8     100      25     9      70                                             1/16     83      0      4      --                                     44a     1       100      0      0      78                                             1/2     100      0      2      80                                             1/4      70      5      4      --                                             1/8      40      10     5      --                                     ______________________________________                                    

Other crops upon which compounds of the present invention have beenshown to be effective are corn and barley.

The following procedures are used to evaluate the activity of thecompounds of this invention for inducing male sterility in corn.

Four rows of inbred variety B-73 are interplanted with two rows ofinbred variety Mo-17. Both lines are planted at a rate of 20,000seeds/A. The chemicals of this invention are applied to variety B-73several weeks later when the last leaf of the plant is just beginning toelongate and the tassel is approximately one inch long and not yetbranched. All treatments are applied with a hand held pressurizedsprayer equipped with a 3-nozzle boom containing D 3 disc/45 core TeeJet cone spray tips. Each nozzle is directed at the row with one placedon either side and over the row. Triton® X-100 surfactant (a trademarkof Rohm and Haas Company) at 0.03% is added as a surfactant. Dosage andcarrier volume calculations are based on rows 36 inches wide.

Pollinating ability of treated plants is measured by crossing theirpollen onto silks of untreated plants and recording the amount of seedset.

Table XII below demonstrates the effect of compounds of Group A, formulaII, of the present invention on the male sterility of field corn.

                  TABLE XII                                                       ______________________________________                                        Example # 8      4      2     1    1/2   1/4  1/8                             ______________________________________                                        16a       --     100    100   100  100   100  --                              ______________________________________                                    

The compounds of Group A, formula II, of the present invention are alsoeffective on barley.

Table XIII below demonstrates the male sterility obtained with one ofthe compounds of Group A, formula II, of the present invention on barleygrain under greenhouse conditions. (Variety Park)

                  TABLE XIII                                                      ______________________________________                                        Example #    1/4    1/8       1/16 1/32                                       ______________________________________                                        16a          100    96        95   88                                         ______________________________________                                    

Table XIV below sets forth field test data which demonstrate further theeffect of several compounds of Group A, formula II, of the presentinvention on the male sterility of field corn (B-73).

                  TABLE XIV                                                       ______________________________________                                        % Male Sterility of Field Corn (Field Test Data)                                     % Male Sterility at Various Dosages (lbs/A)                            Example #                                                                              1/16   1/8    1/4  1/2  1    2    4    8                             ______________________________________                                        43a      100    100    100  100  --   --   --   --                            16a      13     67     99   100  100  --   --   --                            16, K salt                                                                             12     40     100  100  100  --   --   --                            32a      42     84     100  100  --   --   --   --                            30a      --     64     34   100  100  --   --   --                            13a      --     29     59    62   90  100  100  --                            18a      --     --      8    30   80  100  100  --                             5a      --     --     37    52   98  100  100  --                            26a      --     --     70   100  100  100  100  --                            16       Not active at 2 lb/A and below                                        4a      --     --     --   --    12   67   88  100                           14       Not active at 8 lb/A and below                                       ______________________________________                                    

Table XV below sets forth additional field test data which demonstratefurther the effect of several compounds of the present invention on themale sterility and female sterility of field corn (B-73).

                                      TABLE XV                                    __________________________________________________________________________    % Male Sterility and % Female Fertility of Field Corn                         at Various Dosages (lbs/A) (Field Test Data)                                  % Male Sterility        % Fertility*                                          Example #                                                                           1/16                                                                             1/8                                                                              1/4                                                                              1/2                                                                              1  2  1/16                                                                             1/8                                                                              1/4                                                                              1/2                                                                             1  2                                       __________________________________________________________________________    16, K salt                                                                          90 100                                                                              100                                                                              100                                                                              100                                                                              100                                                                              G-E                                                                              G-E                                                                              G-E                                                                              G P-F                                                                              P                                       13, K salt                                                                          27  58                                                                               62                                                                               88                                                                               86                                                                              100                                                                              E  G-E                                                                              G-E                                                                              E G  F-G                                     43, K salt                                                                          90 100                                                                              100                                                                              100                                                                              100                                                                              -- G-E                                                                              G  F-G                                                                              G G  --                                      42, K salt                                                                          16  46                                                                               72                                                                              100                                                                              100                                                                              100                                                                              G-E                                                                              G  G  G G  G                                       32a   82 100                                                                              100                                                                              100                                                                              100                                                                              100                                                                              G-E                                                                              G  G  F P  P                                       30a   52  65                                                                               65                                                                               59                                                                               47                                                                               34                                                                              G-E                                                                              G  G-E                                                                              G G-E                                                                              G                                       __________________________________________________________________________     *E = Excellent;                                                                G = Good;                                                                    F = Fair;                                                                     P = Poor.                                                                

Table XVI below sets forth field test data which demonstrate the effectof several compounds of Group A, formula II, of the present invention onthe male sterility and female sterility of sorghum (Inbred No. 6250).

                  TABLE XVI                                                       ______________________________________                                        % Male Sterility and % Female Fertility of Sorghum                            at Various Dosages (lbs/A) (Field Test Data)                                         % Sterility     % Fertility*                                           Example #                                                                              1/8    1/4     1/2  1     1/8 1/4  1/2 1                             ______________________________________                                        16, K salt                                                                             97     99      100  100   E   E    E   F                             43, K salt                                                                             100    100     100  100   P   P    P   P                             42, K salt                                                                             83     98      100  100   E   E    E   G                             ______________________________________                                         *E = Excellent;                                                               G = Good;                                                                     F = Fair;                                                                     P = Poor.                                                                

Table XVII below sets forth additional field test data which demonstratethe effectiv of several compounds of Group A, formula II, of the presentinvention on male sterility and female fertility of sorghum (Inbred No.7078).

                  TABLE XVII                                                      ______________________________________                                        % Male Sterility and % Female Fertility on Sorghum at                         Various Dosages (lbs/A) (Field Test Data)                                            % Male Sterility                                                                              % Female Fertility*                                    Example #                                                                              1/8    1/4     1/2  1     1/8 1/4  1/2 1                             ______________________________________                                        16, K salt                                                                             35     73      95   100   E   E    G   F                             43, K salt                                                                             100    100     100  100   E   F    P   P                             42, K salt                                                                              9     34      91   100   E   E    E   F                             ______________________________________                                         *E = Excellent;                                                               G = Good;                                                                     F = Fair;                                                                     P = Poor.                                                                

Table XVIII below sets forth field test data which demonstrate theeffect of several compounds of Group A, formula II, of the presentinvention on male sterility and female fertility of barley (VarietyHenry).

                  TABLE XVIII                                                     ______________________________________                                        % Male Sterility and % Female Fertility of Barley at                          Various Dosages (lbs/A) (Field Test Data)                                             % Sterility  % Fertility                                              Example # 1/8    1/4    1/2 1    1/8 1/4   1/2  1                             ______________________________________                                        16, K salt                                                                              32     56     92  99   93   96    75  56                            13, K salt                                                                              2       4      4   8   95  100   100  96                            43, K salt                                                                              4      22     48  77   99   97    94  76                            42, K salt                                                                              3       4      4  43   96  100   100  81                            ______________________________________                                    

Table XIX illustrates the activity of a representative compoundaccording to this invention in corn.

                  TABLE XIX                                                       ______________________________________                                        Sterilant Activity in Corn                                                                       Dosage   %       Height                                    Compound           Rate    Sterility                                                                              Inhibition                                ______________________________________                                         ##STR42##          12  8  4  2  1                                                                        100  97  17  1  0                                                                      18 11  0  0  0                           ______________________________________                                    

Table XX below sets forth field test data which illustrates the activityof representative compounds of Group C, formula XXXI, of the presentinvention on male sterility of barley.

                  TABLE XII                                                       ______________________________________                                        Example   8     4        2    1      1/2  1/4                                 ______________________________________                                        88a       --    100      100  100     58  --                                  89a       --    --       100  100    100  100                                 ______________________________________                                    

Table XXI below sets forth field test data which illustrates theactivity of a representative compound of Group C, formula XXXI, of thepresent invention on male sterility of corn.

                  TABLE XXI                                                       ______________________________________                                        Example          12     4                                                     ______________________________________                                        88a              100    100                                                   ______________________________________                                    

Table XXII below sets forth field test data which illustrates the culminhibition activity of several representative compounds of Group C,formula XXXI, of the present invention on barley.

                  TABLE XXII                                                      ______________________________________                                        CULM INHIBITION (BARLEY) % INHIBITION AT                                      RATE, LB/A                                                                    Example   8     4         2   1       1/2 1/4                                 ______________________________________                                        88a       --    70        70  60      40  --                                  89a       --    --        50  50      50  50                                  ______________________________________                                    

Table XXIII below presents field test data which illustrates the heightinhibition activity of a representative compound of Group C, formulaXXXI, of the present invention on corn.

                  TABLE XVII                                                      ______________________________________                                        HEIGHT INHIBITION, % INHIBITION AT RATE, LB/A                                 Example           12    4                                                     ______________________________________                                        88a               57    43                                                    ______________________________________                                    

Table XXIV below sets forth field test data which illustrates the effectof several representative compounds of Group D, formula XXXII, of thepresent invention as male sterility of corn.

                  TABLE XXIV                                                      ______________________________________                                        CORN, % MALE STERILITY AT RATE, LB/A                                          Example   4      2        1    1/2    1/4 1/8                                 ______________________________________                                        100a      --     100      80   62     85  --                                  101a      100    96       96   74      6  --                                  105a      --     --       100  100    28  25                                  ______________________________________                                    

Table XXV below sets forth field test data which illustrates the effectof a representative compound of Group D, formula XXXII, of the presentinvention on male sterility of barley.

                  TABLE XXV                                                       ______________________________________                                        BARLEY, % MALE STERILITY AT RATE, LB/A                                         ##STR43##                                                                    Example                                                                              8      4      2     1     1/2   1/4   1/8                              ______________________________________                                        105a   --     --     100   100   100   100   --                               ______________________________________                                    

Table XXVI below sets forth field test data which demonstrates the culminhibition activity of several representative compounds of Group C,formula XXXI, of the present invention on wheat.

                  TABLE XXVI                                                      ______________________________________                                        CULM INHIBITION (WHEAT), % INHIBITION                                         AT RATE, LB/A                                                                 Example 8     4     2   1    1/2 1/4 1/8 1/16  1/32 1/64                      ______________________________________                                        89a     --    --    --  --   --  --  35  35    35   35                        90a     80    --    60  --   40  --  35  --    --   --                        91a     50    --    45  --   30  --  10  --    --   --                        92a     40    --    30  --   10  --  15  --    --   --                        93a     --    --    80  --   75  --  75  --    --   50                        ______________________________________                                    

What is claimed is:
 1. A compound of the formula: ##STR44## wherein R₁is a (C₁ -C₆)alkyl or allyl group;R₅ is a hydrogen or bromine atom or a(C₁ -C₃)alkyl group; R₆ is a (C₁ -C₆)alkyl group; Y is hydrogen, X ishydrogen or halogen atom; and n is the integer 1 or 2 and theagronomically acceptable acid addition, sodium or potassium saltsthereof.
 2. A compound according to claim 1 whereinR₁ is (C₁ -C₃)alkyl;R₅ is hydrogen; R₆ is (C₁ -C₃)alkyl; Y is hydrogen; X is hydrogen,chlorine or fluorine; and n is the integer 1 or 2and the agronomicallyacceptable acid addition, sodium or potassium salts thereof.
 3. Acompound according to claim 2 wherein R₁ is a methyl or ethyl group; R₆is a methyl group; and Y is a sodium or potassium cation.
 4. A compoundaccording to claim 2 having the formula ##STR45## wherein Y is a sodiumor potassium cation.
 5. A compound according to claim 2 having theformula ##STR46## wherein Y is a sodium or potassium cation.
 6. Acompound according to claim 2 having the formula ##STR47## wherein Y isa sodium or potassium cation.
 7. A compound according to claim 2 havingthe formula ##STR48## wherein Y is a sodium or potassium cation.
 8. Acompound according to claim 2 having the formula ##STR49## wherein Y isa sodium or potassium cation.
 9. A compound according to claim 2 havingthe formula ##STR50## wherein Y is a sodium or potassium cation.
 10. Acompound according to claim 2 having the formula ##STR51## wherein Y isa sodium or potassium cation.
 11. A compound according to claim 2 havingthe formula ##STR52## wherein Y is a sodium or potassium cation.
 12. Acomposition for inducing male sterility in cereal grain plants whichcomprises as the active ingredient an effective amount of a compoundaccording to claim 3 and an agronomically acceptable carrier.
 13. Acomposition according to claim 12 wherein the active ingredient is acompound according to claim
 5. 14. A method for inducing male sterilityin a cereal grain plant which comprises treating the plant prior tomeiosis with an amount effective to produce male sterility in the plantof a compound according to claim
 3. 15. A method for inducing malesterility in a cereal grain plant which comprises treating the plantprior to meiosis with an amount effective to produce male sterility inthe plant of a compound according to claim
 4. 16. A composition forinducing male sterility in cereal grain plants which comprises as theactive ingredient an effective amount of a compound according to claim 4and an agronomically acceptable carrier.